I think that the series does need a new setting, if only to reinvigorate it a bit - Rockstar run the risk of becoming creatively bankrupt if they keep recycling the same settings over and over again. But at the same time, the setting has to come out of the story. Someone suggested that Miami can only be done with Havana in tow, but I don't see it; sure, there is a large Cuban presence in Miami, but US-Cuban relationships have been pretty stable of late. If I were writing the story, I would make the main character the concierge at a casino hotel. Their job mostly consists of setting guests up with whatever they want, with no questions asked - and they hate it. With no chance of promotion or career prospects, they start selling sordid stories to tabloids. However, their actions trigger a scandal involving a boxer (or maybe an NFL player), and a match that was fixed goes badly - and a local mobster loses out. The player is pulled into a life of crime as a means of making restitution.