Who do you think that the best villain ever is? It could be in a video game or a movie.
In video games I'd have to say Sephiroth. He just embodies the essence of evil and was a truly heinous villain.
In film, I'd have to say Darth Vader. Although he seems tame nowadays, he was really a physical representation of fear in the films.
In comics, the Joker would have to be the best villain. He is the only villain that other villains fear, because his motives and actions are just so crazy and senseless.
Finally, in television I'd say Sylar from Heroes. A great villain.
Old Skool: Darth Vader. Probably a generational thing, but I was in kindergarten when I saw that movie, so he was scary as hell.
New Skool: Hannibal Lecter.
Kain. The man had the chance to save the world, but chose to cast it into ruin for 1,000 years. He vanquished his greatest enemies, then desecrated them by raising them as the very things they crusaded against. That's major.