With three protagonists, the Refugee, the Drug Smuggler and an Undercover Vice Squad Cop who could potentially finds out a plot that is fueling the old war on drugs high up by having the US Government control cocaine shipments with some big pharma companies and elitists along with some some high-ups who take the coke and then spread it out to everywhere while taking a huge cut with some social snarky commentary? Be a great story for a modern day Vice City while still keeping the spirit of the 80s.
Doing drug runs and setting up your own drug operation where it would literally be like a process where you can make some money, no money or a lot if set up right, you would have to win turf wars and basically do your own pick-ups until you can get one of your lackeys to do it.
The Undercover Cop from the DOA, It would open a lot of doors up. It could be a twist or revealed from the beginning. I am wondering if you kill anyone or massacre them - then he might have to be a bit dirty but the good kind of dirty where he ends up teaming up with the Smuggler and the Refugee.
I think playing as the Cop and taking on a US Government supported Central American district intent to kill the Cop and the guys knowing he is a Cop can either kill him or turn on each other in a Mexican stand-off or go up against a Central American Military Death Squad who have taken out all of your Cartel (and who have also beheaded Merryweather members with ease and brutality.), I think a six star appearing only that one time for one of the biggest ending missions (basically escaping from here to the States again).
Logically from a creative stand point, it makes the most sense. Being able to fly to different areas would be nice - Colombia, Cuba, hotbeds where you see real men of power in play.
Packie being a bit of a main character would be a nice nod too.