Wouldn't be bad if the main one was in Los Santos...then the DLC in different cities. But then I'd worry about content being cut.
I loved BoGT and TLaD(<-especially)but I didn't too much care for how you only had one safe house, and you HAD to hang out with both of your friends at the same time.(I got tired of hearing Armando's mouth.)
So say they did have a badass core game set in Los Santos, the next could be in Las Venturas, but you could fly to Los Santos, then one based in San Fierro, there you could fly into both of the other cities.
And say they follow the different character formula, this would allow you to play as your favorite character of the three and still have access to all three cities...
This is my wishful dream haha.
As to how it would actually work, I don't know, I'm not the professional.
I'm the guy who thinks up badass ideas and tells everyone how I should get paid for them.