Well, for one thing, it's already fighting an uphill battle for me by virtue of being an open world game. I've liked many, but it's a genre I've never fully embraced and the GTA series tends to exemplify most of the things I don't like about those games. Riding my horse through the western landscape in Red Dead Redemption is fun, climbing the buildings and leaping from the rooftops in Infamous is fun, even driving across town in LA Noire is fun, but trying to get across town in the GTA games is horrible tedium. I don't know if that has to do with the car controls, or the size of the map, or the fact a police chase can leave you on the opposite side of town from where you were trying to go, or some combination of the above, but it just isn't as hiding the things I hate about open world games as some others have been.
But that doesn't really have much to do with the GTA games, specifically, as it does with the genre. When it comes to GTA, I'm generally not a huge fan of the mission structure. That's obviously not a problem for all missions, but has been hugely annoying for a number of them. Also, I realize that part of any game with role playing elements is starting with low skills/cash and ty weapons/car/etc. and building to better and better stuff, but it feels as though the disparity is too great in the GTA games compared to other series. The early levels of the games are often such a pain to slog through that I've given up before getting to the fun weapons and crazy missions.