+ Great Late game character
+ One of the best chasers in the game
+ Annoying with Harass skill (Tumble)
+ Has an ability capable of interupting spells (Nunu's Ultimate with Condemn)
+ Fun to play with Tumble
+ Can stealth to get into fights (Ultimate + Tumble)
+ Bigger Boobs than several other Champions....

- Very Squishy
- Morbidly Squishy in Early game
- Often can get into trouble chasing into traps
- Lots of people playing her currently

Vayne is a power character late in the game, however in the early stages, she is EXTREMELY squishy. The best setup for the beginning that I've found is getting the Vampiric Scepter early to make it so you can last in your lane (usually Mid), even while taking some damage, and harass the opponent by tumbling towards them to get a shot off, then backing up behind your minions again. You end up staying healed for the most part and can lower their health bit by bit. If you choose to use Ignite instead of Flash, this works great to finish off enemy champions early on as you can harass until half health, get half way away from their tower, Exhaust > Tumble/attack > Ignite > attack/ Tumble again and usually finish them off.

Stay for as long as you can to level up, since your goal should be getting towards your end game setup with both levels and items as quickly as you can.

Greater Quintessence of Desolation x 3

Armor Pen is HUGE for Vayne, makes tanks vulnerable, and squishies die in VERY few hits

Greater Mark of Desolation x 9

Again Armor Pen, one of your more important stats

Greater Seal of Evasion x9
or
Greater Seal of Critical Damage x9
or
Greater Seal of Attack Speed x9

This is going to be personal preference, but because Vayne is so squishy especially early in the game, getting dodge up will allow you to survive encounters and ganks alot better than you'd be able to otherwise. With getting the infinity edge and phantom dancer, you're going to be critting a decent amount, and critting hard, so the arguement could be made to increase crit damage instead, but you can't kill people if your not alive to attack. If you want to be more speed oriented go Attack Speed.

Greater Glyph of Cooldown Reduction x9

Going cool down reduction makes it so you can use what makes Vayne such a strong character much faster. Getting to use your tumble more often, getting to pin a champion to a wall or knock him away from you, or my favorite interrupt a channeled spell like Nunu's ultimate, and especially get to use your Final Hour ultimate more often which generally means death for the entire enemy team.

Offense:
Deadliness is a must 3/3
Cripple is a must (you should be using exhaust) 1/1
Pentiful Bounty isn't needed (you are not a jungler) 0/1
Archmage's Savvy isn't needed (Vayne doesn't do magic damage, so AP is wasted) 0/3
Sorcery is a must 4/4
Alacrity is important but mostly used to get you down the tree 3/4
Burning Embers isn't needed (you don't need AP from this) 0/1
Archaic Knowledge isn't needed (Vayne doesn't do magic damage and you don't get madred's) 0/1
Sunder is a must 3/3
Offensive Mastery isn't needed (you don't need to be the best mob killer, you want to kill champions) 0/2
Brute Force is a must 3/3
Lethality is a must 3/3
Improved Rally isn't needed (you don't use rally, at least I hope you don't) 0/1
Havoc is a must 1/1

Defense:
You'll be putting 9 points in here if you went the Dodge route for runes, if you went crit or attack speed, go Utility instead
Resistance and Hardiness you'll put 4 points into these skills
Evasion 4/4
Nimbleness 1/1

Boosts Dodge and helps you get away if your in trouble

Utility:
I'll just talk about the skills I suggested...
Perseverance increases health and mana regen (makes you less squishy and can use abilities more often)
Good Hands I put a point here to move down, and because being dead less is always a good thing, especially late in the game
Awareness getting more exp during the leveling up phase gets you to 18 faster which is needed badly for Vayne
Greed extra gold for items since Vayne is so item dependent

All of the items I've listed have sub-items, so get something when your back at base

Vampiric Scepter - Helps you stay in your lane early, don't waste gold on pots, and turns into Bloodthirster later

Berserker's Greaves - Movement speed and Attack Speed, good for running away or chasing to finish

*The other option I've been considering is Ninja Tabi boots, they get armor that helps you since Vayne has low health and is VERY squishy, plus increase your dodge. With these boots + 9 Runes for dodge and the mastery abilities Vayne can get up to 22.75% chance to dodge physical attacks (All auto attacks do physical damage), and increase movement speed by 10% for 5 seconds every time you dodge. This combo has saved my *** more than I'd like to admit.

Phantom Dancer - Crit, Attack Speed, and Movement Speed, helps alot early on for several reasons

Infinity Edge - Big boost for AD, along with Crit chance and moving Crit damage from 200% base to 250% base (once you get this, you become pretty powerful compared to other characters)

Black Cleaver - Good AD + Attack Speed with Armor Pen stacking debuff (great overall weapon)

Bloodthirster - Base of 60 AD with 15% Life Leech, stackable to 100 AD and 25% Life Leech and the best part, the passive is NOT unique so two of these can end up being 200 AD and 50% Life Leech

Last but not least....

Trinity Force - Get this by selling your boots and replacing them with this... It's the final upgrade that brings crit up more, movement speed will get some boost to soften the blow of losing boots, plus more health/mana and the best part is every time you use Tumble (should be often) you do more than 100% more damage the next attack

Get Tumble early to harass. Condemn as a utility to push back to get away, or pin to a wall to kill. Max Silver Bolts ASAP for True damage and bonus damage every few attacks, and get Final Hour every time you can, this skill is your "I WIN" button

Exhaust - Great early in the game to help get champion kills (saves your *** later for 1vs1 against assassins that can stun you)
Flash - Good for getting away from trouble or jumping into it
Ignite - Good for finishing off enemies early, or slowing down healers
Cleanse - An option for people who get locked down alot and just need to get away
Ghost - The partner to Cleanse for a quick get away

With this build I usually end up dominating late game and can often kill most of or all of the enemy team very quickly. Your able to 2-5 hit almost anyone, and I often crit for over 1400-1500. With Trinity Force and after a Tumble it goes even higher. Every time I actually get to upgrade anywhere near the full build's items, people almost always start crying about Vayne being OP, which is funny because they should have seen me before the nerf this last patch applied.

If you're looking for a fun character to play with that can single-handedly turn the tides of a match during mid to late game, you'll love Vayne. She's fun to play tumbling around all the time, and it's great to see huge numbers popping up from the huge crits. Bloodthirsters + your Crits = HUGE heals going constantly, so the only way to take Vayne down late in the game is to stunlock her or have the entire team focus fire on you first.

LAST TIP: Although you can win almost any 1v1 matchup. Try to never be the one to initiate fights if you can help it. You're a finisher, not a tank. If you're not being targeted right away you can take out the whole team, so use that to your advantage.

Hope you liked the guide... I will try to add to it if there's any questions later...

PLEASE tell me how you play vayne and any suggestions, but try out the build and see how it works for you, I've been getting great results.

*** PLEASE VOTE AND RATE THE BUILD IF YOU LIKED IT! ***

*Edited build to change 2nd Bloodthirster to Trinity Force, and added Dodge Rune/Masteries/suggestion for Ninja Tabi boots to increase survivability

*Possible changes later, for PVP heavy builds people have suggested Banshee's Veil, but Vayne is a finisher, and should NEVER start a fight so I'd rather have more offense and defense against physical attacks over blocking a harmful spell and some more stats. We will see later as I continue to try and refine this build.