I know they spent so much money and effort on all of the finer mechanics, but I feel like there are more fundamental flaws that hurt it.
Lethality is far too high.
San Andreas let you spend upwards of 15-20 minutes exploring before your recklessness got you in trouble. GTA V can kill you minutes, whether it's because of the hypersensitive police in the city or your bike capsized down a small mountain. I like a challenge but sometimes I just want to explore without worrying that deviating from the acceptable path just a little bit would get me killed. That, and even with a low health bar, the campaign proved to be quite easy.