Kefka - He works his way up from dick underling to petty god and ruler of the world while you're busy trying to stop the evil empire. Then the second half of the game is spent recovering from the mess he made of the planet before finally defeating him. So many moments where his evil self shines in ways that other villains can only dream of. (Final Fantasy 6)
Kane - Kane is a charismatic, scheming bastard the likes of which are truly rare. He's three steps ahead of the good guys and two steps ahead of his own organization. Somewhere along the line, you get the feeling that he's just in it for his own designs, some inner vision we may never fully understand. Everyone else (including alien invaders) are just pawns for him to shuffle around the board, and there is no piece too valuable for him to sacrifice to reach his goals. ( Command & Conquer )
Kerrigan - She *was* one of the good guys, and a fun character all on her own. Then the evil aliens took her, changed her, and made her one of them. Her new peers didn't even know the full extent of what she had become. *She* did, and there was none of that silly waffling over shreds of her former self or cliche' redemption. She knew exactly the person she use to be, and it never slowed her down once. She used her cunning, power, and even former comrades and friends in her relentless drive to conquer everything in the name of the Swarm. How many video game villains have you controlled through their rise to power? Where at the end of the game, they stand before the combined might of three opposing factions and proclaim themselves to be 'Queen ***** of the Universe'? ( Starcraft )
Runner up - GLaDOS