One major issue for me is car spawning. Why is it that with all the power in the 360/PS3, the developers couldn't figure out a way to fully randomize the vehicles? We shouldn't have to suffer through this anymore. There's nothing else in the game that spoils the buzz as much as running around trying to find a decent car and only having Humvee's and CRX's to choose from.
The friendship system should also be tweaked. Or at least give the user the ability to turn it off or on once a friend's unique service is unlocked. Having to keep Jacob, Packie, Brucie, Roman and Dwayne happy is a real pain in the ass.
That's all I can think of that doesn't require a true revisitation on behalf of Rockstar. It's a great game, this GTAIV, but it has some serious issues that hopefully will be addressed in the DLC.