Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
Vayne, the newest member of the League, is an agile and cunning huntress, relying on swift hit and run tactics and also sneaking. Usually, when Vayne gets the "lowdown" on someone that isn't expecting it, odds are that that person isn't getting out alive.
With Vayne, you'll want a lot of attack speed and armor penetration. Early game, she still hits hard with her "Tumble" bonus, granting her +75% (at 5th level) bonus damage on her next attack, but really this champ relies on "excess". If you can have more, then by all means get more. Later on, when you unlock Vayne's "Silver Bolts", attack speed becomes much more important, since every 3rd CONSECUTIVE attack deals bonus true damage, 1st level being 40 dmg + 4% of the enemy's life total. The faster you attack, the more often you can dish out this damage. Armor penetration goes without saying; You can't stay in the fight for long, so you have to end it quickly. This will do a good part of the work for you.
Basically not much to say about the masteries except that you want to get all the attack speed and damage you can get from the list. Havoc is a must and I urge you to get it. For the Utility list, 1 point in "Utility Mastery" is good to keep those monster buffs going just a little longer (most of the time, these buffs are stolen :D)
At 1st level, Vayne is ultra squishy and slow, starting with only 310 movement speed (unless you change the rune build and/or mastery build). "Doran's Blade" is a decent starting weapon, since it gives you extra damage (good for Tumble), life steal (minimal but still welcome) and a bonus 100 HP, which Vayne desperately needs at the start.
Afterwards, if you play your cards right, you might get First Blood and that bonus gold can help make you a bit faster. If this is the case, Boots of Speed are needed first! Afterwards, upgrade to Berserker Greaves for extra attack speed. Now that speed is covered and you are doing pretty good so far, save up to buy a BF Sword. If you're struggling for cash and need an extra push, buy a dagger and wait for more GP until purchasing the Black Cleaver. You absolutely need this bonus damage, attack speed and armor reduction that the Cleaver gives you. With it, your "Silver Bolts" will trigger faster, your Tumble will deal increased amounts of damage and after rapidly firing at the champ, if he doesn't retreat, he's surely gonna die (exceptions apply). Even though it may seem tempting, don't reach for Infinity Edge or Bloodthirster first. Trust me, after a little while, you'll be swimming in money. Patience is a virtue.
Once you've purchased the Black Cleaver, you are now hitting faster and harder, but now we gotta work on pursuit gear, which the Phantom Dancer does quite well. It's attack speed bonus (+55%!!!) is astounding and will help Vayne pump out her Silver Bolts so much faster. Also, movement speed for chasing. Critical is cool too, but we're not focusing on that... yet.
Now we're getting to the REAL gear that makes Vayne a "Terror of the Night". Madred's Bloodrazor is, hands down, the most useful weapon that she can have in the game. Too many times have I been successful with the build and the opposition would surrender before I could even buy this gem, but whenever I could, it was time for some killing. With the bonus Attack damage and speed, Vayne's abilities shine even more (armor too, but more of a bonus than a necessity). But the best part is the "4% of max HP in bonus damage" that it gives off on EVERY ATTACK!!! With your Tumble comming back every 2 seconds, damage is something that Vayne gives out in thousands, and this item here is very important.
Finally, if the game has gone on for this long, you'll probably have a lot of money, which you can spend as you want, depending on the opposition, some items might be more beneficial that others. I like the Bloodthirster, but the choice is yours.
*NOTE: Alot of people have been taking Sheen as their 3rd item (before black cleaver). I admit that the bonus dmg is cool after each ability, but the only actual benefit that this item brings to Vayne is the extra mana. That's it. Also, early game if you're having a hard time laning against your opponent, buying a Potion or two wouldn't hurt. Also investing in a Vampiric Sceptre early on too is good.
Vayne's most treasured ability is Tumble, which allows her to roll towards your cursors' location and makes her next attack deal bonus damage. This bonus damage depends on your base attack damage, so getting extra damage is a must, since Tumble comes back every 2 seconds (at 5th level). Anytime you can add a level to Tumble, please do (unless you have the option of taking a level in your Ultimate)
Silver Bolts is important, but not at first. You'll want to wait until level four before putting a level into it. Afterwards, it is the last ability you should put points in.
Condemn is both a great "fight starter" and a getaway plan. If you're waiting in the jungle next to a wall and an enemy goes by, you can shoot him with Condemn to deal damage and extra damage once he hits the wall. Plus he's stunned. During this time, Vayne can dish out a Tumble shot and another shot. By the time he gets out of his stunned state, you'll be dishing out Tumbles and Silver Bolts damage. Very useful when running away, since it knocks back the pursuer. If that doesn't work, flash out of there.
Last, "Final Hour" is great for finishing off champs or for evading a multitude of problems. When activated, your Tumbles render Vayne invisible for 1.5 seconds, which isn't a lot, but can get you out of a bind like Fiddlestick's life steal ability and many others. Also during the Final Hour, attack damage is increased, so is your movement speed while moving towards enemies.
Exhaust is good for keeping your target from escaping (obviously). Early on this is good too, since people tend to underestimate Vayne's damage-dealing capability. If in the middle, one-on-one is an advantage. Rolling in for a shot from time to time, then doing a final roll then Exhaust to finish it off.
Flash is the spell Vayne relies on for getting her out of trouble. Using it to chase someone is pointless, since you'll be left with no means of escaping if you're in a fix.
NOTE: Ghost is just as good here and can replace exhaust. NEVER REPLACE FLASH!!!
All in all, keep distance, roll often and retreat, get some extra attack speed and damage and everything should turn out "A-OK". Late game, people will come to fear you since you deal ridiculous amounts of damage, which will likely lead them to try and gang up on you any chance they get. Try and anticipate this and stay far from a whole group of enemies. Vayne can do good against chasers, so use the jungle to hide and stun them with Condemn, then finish them off with Tumbles galore.
Thank you for reading my 1st character build and I hope you enjoy playing Vayne as much as I do. Happy hunting!