Winner and still champion: Josef Stalin. Evil is as evil does, and nobody's done more than he except in the furthest realms of fiction.
Runners-up:
Dracula (how many villains today are Dracula based?)
Hitler (for the sheer popularity of his minions as cannon-fodder)
Emperor Palpatine (subtle...)
Vader (of course)
Doctor Doom (because he's right, you doddering simpletons!)
The Borg Collective (if you find the concept of a Borg Queen distasteful, just think of her as an avatar of the Hive Mind. Hence every time she shows up on Voyager she's being reassembled from spare parts...)
Gul Dukat (off Deep Space Nine - a more twisted wretch of a man I have yet to see)
The Mayor (from Buffy, because he's so darn nice!)
Mobius (from Legacy of Kain series of games, because he's a despicable bleeper)
Cell (from DragonBallZ - he looks cool)
Buu (kid form, also from DBZ, because he's so pointlessly evil he blows up planets while he's still on them)
... and the People's Republic of Haven (from the Honor Harrington series by David Weber - an interstellar nation whose economy has been set up in such a way that they have no choice but to conquer everyone in sight)
Can't think of any more just yet...