Liquid Snake (in MGS1), probably. Guy's the best played villain in all of video gaming (this is objective, don't disagree), and Cam Clarke's performance just heightens his already great role to new levels of greatness. There's not one qualm I have with how he was handled, and not one error I can find with the character. He's perfect and there's no denying that.
Honourable mentions include Rugal Bernstein, Wolfgang Krauser, Dracula, Sigma, Ganondorf and I suppose King Dedede, among others that I have forgotten.