San Andreas was my favorite also.
It was the customization I'm sure.
For me, the next logical step in the GTA franchise would be to incorporate RPG (at least westernized) systems deeply into the game.
Elaborate on the customization seen San Andreas, clothing, body form, etc, and extend it to other things such as, leveling up weapons, driving, car mechanical skills, stealth, burglary, brawling, whatever, allowing for different game styles* and the unlocking of new features (a high car mechanic skill would allow you to mod your car with better gear progressively, for instance) giving the feeling of progress and goal.
*allowing the player to choose how he wants to complete the game, by force, by driving skill by drug dealing or by charm.