This is gaming discussion so I assume you mean best gaming villain. I always like Saren as the villain of Mass Effect. His belief that he was actually saving the universe humanised him to me in a way a lot of bosses don't. No one ever starts off on an endeavour thinking that they're going to commit evil, they will have a string of reasons and concessions which led them to the point where they become the enemy or start shooting cool Spectre selectors in the dome. That stuff ain't cool, yo.
In all villainy I would of course say Two face. Being my avatar aside, I've always liked the duality of the Two Face. I remember reading a comic ages ago and Batman was captured by a gallery of some of the worst villains in Gotham, one of whom is Two Face. I can't remember the specifics but they're probably wringing their hands with lascivious looks of pleasure as they consider how they'll dispose of Batman. The dark knight then asks Two Face to flip his coin whether he should live or die. Agreeing, he flips the coin and Batman wins the toss as it were. Two Face then beats down everyone else until they release Batman, with an iconic image, at least to me, of him choking the penguin asking for the key or whatever is going to be used for the unlocking. This was a bad guy, with bad guys, who would beat the snot out of them instead of killing his arch nemesis, on the toss of a coin. It's very unlikely that another villain will intrigue me as much.