I think it says something that Rockstar is calling this "Grand Theft Auto IV" instead of 'GTA6'. They acknowledge that Vice City and San Andreas are spin-offs of the same GTA3 game, so we can expect GTA4 to be different.

They're raising our expectations by giving it the label of being the 4th GTA. I highly doubt there'll be as considerable of a leap between GTA2 to 3, but there better be somethin'.