Vice City easily (game + main character).
Haven't played enough of IV for it to be even considered yet, though I am expecting it to at least be ahead of every other game bar VC.
I wasn't keen on them going the Eastern European route either at first, but after playing it I do think Niko is a great main character. Don't know if he will overtake Tommy Vercetti, but since I love the whole Italian Mafia scene in general it's not a very fair competition in the first place.
The music is about the only place where I feel IV is considerably behind other versions, but that's only as a result of the game not having an iconic culture to latch onto as VC and SA did.