The idea of doing a spin-off or sequel featuring one (or more) of these characters intrigues me as well. I'm thinking that one way to do it could be to merge some of them into one. For example Miles Morales and Ben Reilly. Introduce Miles in the TASM universe and have him become the Scarlet Spider, so as to differentiate more clearly between him and the actual Spider-Man - and also to avoid the hassle of the clones. And then add some of Reilly's characteristics. I guess he would be more of a legacy character. I don't know, I'm just thinking out loud.
Doing Spider-Man 2099 could be really cool too, even if I doubt Sony have the balls to do something like that. But I think that at least visually, it could be stunning. They could also make it a crossover with Garfield's Spidey. I imagine something a la the "time rip / time travel" in DOFP. Spidey swinging around contemporary New York City, suddenly ends up in a futuristic city looking like something out of GOTG, teams up with O'Hara to set things right. Very simplified of course, you could do it a million different ways, but I definitely think there are plenty of opportunities with these characters, if they really want to dig into the universe and expand it.