Easily the most regularly irritating flaw in the GTA series to date has been the cock-eyed targeting. GTA IV uses a very different system, but GTA's III, Vice City and San Andreas were cursed by random target-selection, combined with a sickening camera that lurched wildly between enemies.
You could never quite predict whether hitting the R1 button would target the guy dead ahead of you (and shooting at you), the closer one right behind you(shooting at you), the one nearest (but not shooting at you) or the innocent bystander (not even looking at you). But you could be fairly confident that you'd end up targeting the wrong guy whatever happened.