Okay — this may seem a little obvious to someone of my generation — but the defining film villian HAS to be Darth Vader, right? And I mean Star Wars & Empire Vader, not RotJ and GOD FORBID the more recent films' incarnation.
Sauron from LotR was too disembodied to have enough sense of presence.
Hannibal Lecter perhaps runs a reasonable second.
I will also give props to Alan Rickman's portrayal of Severus Snape in the Potter films. I guess we'll have to see whether Book-7 gives him any redemption or not.
What about the "Alien" from "Alien" and "Aliens"? They were tough, smart and deadly — though I'm not sure they were evil. But don't count the third movie because it was so wretched — though I'm sort of surprised to say that AVP was kinda good campy fun.