Ghost - I choose ghost to pursue dying enemies. I also use it to escape. I prefer this over flash because flash is harder to use and Flash's mastery point is much further down in the Utility mastery tree. It combos well with Exhaust.

Exhaust - I select exhaust to slow my enemies and deplete their armor. This works well with Vayne, plus it can help you escape. It combos well with Ghost.

Since Vayne is AD Carry, I believe she should be full offense in masteries. She's a little squishy, but I think that can be helped by buying the right items in the right order.

Vayne's gear is pricey, she has to buy THREE BF Swords, so I add that Utility Mastery point in 1 extra gold per 10 seconds.

I choose condemn first because it has offensive and defensive qualities. Offensive because I can put a lot of damage down if an enemy gets too close to a wall. Defensive because it can save me from a 1 v 2 gank as I retreat to my turret.

Rune Build:
I believe enhancing her fundamental qualities is the best approach. Therefore, I select attack speed, armor penetration, and attack damage. You can never have too much of any of these with Vayne.

Item Purchase:
Youmuu's Ghostblade is easy to build because it has so many small parts. You gotta build this first, then add some attack speed.

To me, her #1 item is Bloodthirster. I think it is critical to be able to quickly refill her health mid to late game by hitting enemies or minions. Unfortunately, this only has two parts, one that is cheap and one that is expensive. I get the life steal pretty early on to add longevity.

I also enjoy movement speed so I buy the Boots of Swiftness (enhanced movement speed 3). I don't like when enemies slip away with 10% hp because they're faster than me. Conversely, this speed, plus roll, plus ghost make Vayne difficult to chase after. I prefer these boots because I select 4 points in Alacrity (offense - attack speed) and I have 9 alacrity runes. I start off with a fairly decent attack speed, so I don't use Berserker's Greeves, for now.

I buy the Heart of Gold to a) make Vayne less squishy, and b) get gold faster. I took this directly from watching the professional tournaments where they sometimes grab two Heart of Gold.

I usually play mid for the additional gold and XP.
I take it easy early game, focusing on accumulating gold.
I farm creeps when they're available and our jungler hasn't disposed of them.
I don't play on Ventrilo or in arranged teams, but I would like to if I could find dedicated players like myself. I just built a brand new, high end gaming PC as of 9/1/11. Hit me up in game - Dirtnap.

Near the end of the game, you can take down anyone WITH ONLY AUTO ATTACK since she automatically pursues her bleeding enemy's at a devilishly fast 40% speed boost. I save ult + exhaust for team fight insurance. E + Q are enough to end any caster's life in a few short seconds. I don't see the word 'stun' anywhere on Vayne's E, but the net effect is that they get stunned if they hit a wall after your E. Combined with her attack speed and massive damage, the enemy should barely be able to get a flash off, much less continue breathing. If they flash, simply ghost, chase, and kill. But don't chase into enemy territory unless at least 3 of the other 4 champs are dead. Otherwise, you may find 4 other champions with your name on their blades.

It's difficult to be patient enough in team fights to engage after others on the team have, but I have learned this lesson the hard way by giving up my life too soon. Therefore, I usually hide in a bush, ult, and attack the casters when the time is right. Noobs think this is being passive, but they don't play squishy Vayne. Not only that, but hiding in the bush gives invisibility, ulting adds an additional 1.5 seconds of invisibility, combined with rolling gives Vayne a surprise attack that's something fierce. Plus, once the enemy team has committed and run towards my base, I can attack from behind, pushing one of them into our turret's range for an assisted kill.