Vayne is a very powerful champion in LoL from early to late game. However with this power comes responsibility. She has very little durability and is often the very first person first. And that's even before mentioning that she is one of the hardest champs to learn how to play. So, I'm hoping that this guide helps some people get a little bit of an edge on their learning curve and maybe provide a viable guide to older Vayne players.

Vayne is an assassin character who excels at leaping from the side of the lane and exploding enemy champions in a few hits. However in the hands of an expert player, she can serve an even more important function.
Vayne has one of the highest DPS capabilities in the game, allowing her to quickly bring down enemy carries with little to no help. And her Silver Bolts allow for massive damage against any target, meaning that even tanks fear her because they know that they're just as vulnerable.
So, while Vayne won't really be the person that you have to worry about backdoors from, she is certainly a person that will keep the enemy team in clumps or near their base; preventing mentioned backdoors, ganks, and dragon/baron runs.

Greater Mark of Desolation- This is probably my favorite rune for AD based champions. This gives you a lot of early game damage that won't fizzle out as the game goes on. That's why I prefer them to Greater Mark of Attack Damage. As for Greater Mark of Attack Speed, they're a more viable choice for Vayne than for most other champs. However, I still lean towards the armor pen because there are plenty of items that give attack speed; so you can make up quickly in game. However The Brutalizer and Youmuu's Ghostblade are the only real viable choices for armor pen you have once you get in game, so any bonus you get to these stats in the metagame will put you at an advantage.

Greater Seal of Armor- The cool thing about these runes is that they are just as effective against champions as they are against minions (and I'm going to tell you right now, minions will do more damage than you think with as little health and resistances as you get). I've seen Greater Seal of Attack Speed here before, but the bonus from these are too small to be worth the precious ip and slots. If you still think this is the route to go though, by all means go for it; it's just a personal preference on my part.

Greater Glyph of Cooldown Reduction- CDR. This is great on just about any champion that you play, but especially good for Vayne who relies just as much on her Tumble to deal damage as her auto-attack. Greater Glyph of Magic Resist is acceptable here for a more 'tanky' metagame.

Greater Quintessence of Attack Speed- This is where I get my early game attack speed. This gives me a nice boost without forfeiting the power of armor pen marks. I have personally never tried interchanging the quints and marks, however I see no reason why it can't be done if you prefer more early game attack speed. Greater Quintessence of Health is also a great option here.

Note* Vayne is not a very mana hungry champion. Her Tumble does not cost a lot of mana and she has relatively high natural mana regen compared to other AD based champions. So it's my opinion that Greater Seal of Replenishment aren't needed. However if you just find that you never have mana, I would probably advise replacing the Greater Glyphs of Focus with them over the Greater Seal of Armor. This is a VERY optional choice that depends SOLELY on personal preference and gamestyle.

Standard 21-0-9.
I prefer this setup because it increases my early game power and helps with the transition into the mid and late game as well as my last hits. While it's true that this tree is considered underpowered by most players, the defense tree doesn't do much for Vayne since the bonuses are too insignificant to matter when combined with her already low durability.
Utility is a way to go and it's true that I played with it for a while. However in the end, Vayne already has pretty low CD, especially when compounded by Greater Glyph of Cooldown Reduction. So getting 9-0-21 instead of the early game presence provided no noticeable difference in the late game and heavily affected my early game performance.

Note* These are about to get a HUGE change. I plan on updating this as soon as I find out the specifics of what bonuses are going to be available.

I chose
Exhaust-A great offensive AND defensive ability. It has several uses and makes 1v1 a champ or knocking down the effectiveness of a particular carry in a teamfight that much easier. This is also one of my all time favorite summoner spells because of its multiple purposes and because it's such an end-all decider of a lot of fights.
Flash- Vayne doesn't have a lot of escapes other than her stealth from Final Hour and Tumble, and even that doesn't last real long. So having something for all levels is nice.

Other good spells:
Ghost- While it's not as good for a chaser as it is on other champions because of Night Hunter, Vayne has a relatively low movement speed and is easily caught when trying to run away.
Cleanse- Vayne is VERY squishy, so every little second that you're not stunned or CCed is nice.
Teleport- I would only advise using one of your slots for this if your team is really good about warding. This lets you span great distances to get to the teamfight before it's over. Otherwise for turret defense purposes, leave it to the tank or another character less dependent on these abilities to be able to succeed.

My build focuses on giving a few situational branches and options throughout the game to make sure that no matter what the circumstance is, you have the ability to adapt. I do this by getting items that have the capability to be built into several different items with varying effects and gradually building up bonuses so that you aren't too vulnerable during any stage of the game. It also guarantees that at any point in the game, a top tier item is available for less than 1800 gold, allowing you to branch out to fit your needs. This is not a concrete build; it is a clay one.

Doran's Blade- I start with a Doran's Blade because it gives a decent bit of early game damage with some survivability. It also gives a small amount of life steal; 3%, a number that will be explained later. I guess if you're confident you can get Boots, but this is personal preference. I like the durability that the blade will give me.

Boots- Boots are almost always situational items. I usually get Berserker's Greaves because the early game bonus to attack speed in addition to movement bonus really lets loose your Silver Bolts. I don't really get any real tenacity items, but if you don't feel safe because of CC, go ahead and get Mercury's Treads.

Pickaxe, Recurve Bow, or Emblem of Valour- This next item is where you really start to figure out where you need improvement. Firstly ask yourself, 1)Am I doing a decent amount of damage with my auto-attack so I can farm well and deal suffecient damage to the enemy, 2)Am I constantly recalling because I have no health, 3)Am I facing off mostly 1v1 with one enemy over and over, and 4)Am I fighting one of the beefier characters on their team?
If you answer 'no' to the 1st question and 'yes' to the 2nd question and/or 3rd question, consider buying the Pickaxe for early, cheap AD boost to give you an edge. If you answered 'yes' to the 4th question, buy a Recurve Bow to increase the proc on Silver Bolts and whittle down their health faster. If you answered 'yes' to the 2nd question or 3rd question, buy the Emblem of Valour. This will increase the chance that you will come out ahead 1v1 and increase your lane survivability. After you ask these questions and buy the first of these items, reprioritize, and get the next item. Then finish the early game with getting the last one. This gives you a variety of bonuses that Vayne needs for about the same price as one of the more expensive items that would only give you an advantage in one area.
Note* With Emblem of Valour and Doran's Blade, you get a total of 20% lifesteal; the same amount as Zeke's Harbinger

Zeal, Madred's Bloodrazor, or Zeke's Harbinger- Now the mid game has started, ask these. 1) Do I need survivability, 2)Is the enemy team mostly tanky or squishy? If you answered 'yes' to the first question, go ahead and purchase Zeke's Harbinger for the health regeneration and increased attack speed. If you answered 'no' to the first question and 'tanky' to the second, get Madred's Bloodrazor. This will let you cut through lots of health and at rank 5 Silver Bolts, you deal out 20% of their health every 3 hits. If you answered 'no' to the first question, and 'squishy' to the second question, then get a Zeal to increase your movement speed, attack speed, and crit chance. This will let you run through squishy health fast.
Note* This normally where I sell my Doran's Blade

Phantom Dancer or Madred's Bloodrazor- At this point, if you bought Zeal earlier, upgrade it to a Phantom Dancer to ramp up damage output. If you bought Zeke's Harbinger earlier and realize that you're still fighting tankier champs, go ahead and purchase Madred's Bloodrazor. At this point, you've either bought Zeke's Harbinger, or you probably don't need it. If this is the case, there's no problem with sitting back with Emblem of Valour for the rest of the game.

Infinity Edge- This is a viable item choice if you went the route of getting the Zeal and Phantom Dancer over the Madred's Bloodrazor. If you got the Madred's loodrazor, chances are, there's just not enough time in the game to buy this too. This compounds on your crit chance from Phantom Dancer and give you a nice boost to AD in the process.

Wit's End- This item gives a lot of attack speed, allowing for more Silver Bolts procs and more DPS from your basic attacks. It also deals 42 magic damage per hit, allowing for an effective counter to high Armor builds.

B. F. Sword- A lot of builds get this very early in the game. This is a very powerful item; especially for the gold cost. However while I don't condemn it, I will say that unless you're getting fed, you're going to have to save up for it. If you are fed, then by all means pick this up early! But since this is rarely the case, buying a few, lower priced items leaves you in a better place during the early and transition phases of the game.

Bloodthirster- This is a great lifesteal item and I like it a lot. However this item gives 15% lifesteal that only increases to a max of 25% (only 5% more than Zeke's Harbinger) under ideal circumstances. Meanwhile, items that give attack speed help benefit Silver Bolts. So, unless you're getting really fed and could afford that early game B. F. Sword, I prefer Zeke's Harbinger

Sheen and Trinity Force- These items give very good burst damage to Vayne. However, remember that it only multiplies the original base AD (which is 109 at level 18). So at most, you get a bonus 218 damage for a mana cost before armor reduction. During the end of the game, this bonus is just too small to be worth the 4k gold shelled out to Trinity Force. As for its other effects, Vayne doesn't need a slow because of Night Hunter, and while it does give a lot of stat bonuses, only a few are really useful to Vayne, so the rest of the gold you spent on it is pretty much wasted.

Defensive Items- At any point you feel necessary, get a defensive item. Some of the best for Vayne are Guardian Angel and Banshee's Veil. NEVER GET Thornmail FOR VAYNE. She doesn't have the health to make the return do any worthwhile damage. If you need armor, you're better off getting Guardian Angel or even Sunfire Aegis.

Vayne is unique in that she only deals one type of damage, physical. Silver Bolts will let you get through any armor. THERE IS NO WAY TO ITEMIZE AGAINST THIS SKILL! However, there is a way to itemize against Vayne. Thornmail. This item will bring down Vayne very quickly and armor will reduce her attacks to nothing. So what's the best way to counter it?
There isn't really a way to do it with Vayne, the only thing to remember is to NEVER, EVER hit that champion 3 times and proc Silver Bolts. This is because Silver Bolts is considered an on-hit effect and thus will be returned as damage to you, and since that champion with Thornmail will probably have lots of health, you WILL be obliterated by it.
The other thing to remember, is to NOT purchase Madred's Bloodrazor or another on-hit item like Wit's End or Sword of the Divine because these will also be returned as damage to you and thus will wittle your already low health to nothing. Instead, purchase high AD and critical builds coupled with MR items like Banshee's Veil to reduce the magic damage returned.
Note* The champion with Thornmail is probably the tank, so don't focus them down unless they're the only one left or you catch them on their own.

I prioritize Tumble over everything else because it does a lot of damage throughout the game while being very easy to hit and use compared to her other skills.
I take a point in everything else early to get some Utility from Condemn and damage from Silver Bolts.
WHY DON'T YOU START WITH Condemn? IT DOES A TON MORE DAMAGE!
Well, you're right. It does, so long as you can ensure a pin every time. Which is not only a difficult feat on its own, but nearly impossible in the open lane. So for those who ignore this and max if first anyway, keep in mind that everytime you miss a Condemn is a long CD, twice the mana, and damage that you would not have wasted had you taken the point in Tumble instead.

So, overall, Vayne is a very effective champion capable of extreme critical damage or a true damage barrage from attack speed.
This and her ability to bring down a multitude of enemies makes Vayne one of my favorite champions as well a powerhouse to those who know how to play her.
With all that said, please leave any comments or criticisms below.
Thanks for reading and good luck on the Rift!