I made this blog from a comment I made about the Conduits being wiped out from existence.
Essentially, Cole just used the RFI to save humanity but in the prossess, killed all conduits (including himself). Due to all that... there's no way there's gonna be Cole coming back or atleast creating another hero for the series because all Conduits are gone. Sucker Punch pretty much killed the franchise, leaving no "real" opening for sequels. Unless they were to involve supernatural stuff or "folklore" then maybe but that's just screwing it up the cool parts of Infamous. Though, if possible; some of the First Sons that didn't have the conduit gene might create a new gene with the same ideas. Seems unlikely but possible. Also an evolution might occur to some conduits that might've became more than conduits, like the mutants from the X-men merging with the conduit gene. That also seems unlikely because of the conduit gene is pretty much the same thing as a Mutant. A conduit under a barrier is possible but wouldn't work.
The only way they could make a sequel is that if it had something to do with time, supernatural (not like vampires, I'm talking about witchcraft or reincarnation and stuff), or folklore (with gods of ancients) and that's just f-cking it up big time (no joke). Right now, I think Infamous is over... but wait, due to the new game "Festival of Blood", Cole Macgrath may still be alive but will no longer fight Conduits and instead could fight supervillains close to the classic time supervillains (forced mutation, extreme technology, supernatural reasons, and Conquerors from outer space). This is the closest you could get for a sequel but still would be screwing it up.