Now judging by both endings of inFamous 2, it APPEARS that Cole's jouney more than likely ends here.
However, this in no way implies the end of inFamous! Especialy when I replayed inFamous 1 =D
Torwards the last missions, spicificaly the one in which you are locating the Ray Sphere using the helicopter, John mentions that he "copied ALL of Kesslers notes" and also says QUOTE "You don't think the government will try to recreate the Ray Sphere?"
Now, true all Conduits were wiped from the earth (Considering that the hero side of the story is in fact canon), but Ray Feild Radiation had to get to the earth somehow.
I suggest simply that if Sucker Punch chooses to make another inFamous, they may not use Cole and use a sudden Solar Flare as an excuse (hence the origin of the Ray Feild Radiation that creates conduits) to kick start the next game, using the government to "unlock" these new conduits.
The other possible choice is that the flare somehow ressurects conduits that were killed by the RFI, incase Sucker Punch decides to keep Cole. But this may include the Beast (if his body isn't completely gone).
The plague might not be a problem in the third, because the gov't likely knew what originaly caused it due to John's suspicions, thus over a period of time creating a method to avoid exposing potential "Biological" conduits from becoming a second plague.
Side note: John's suspicions comprised mainly the fact that the gov't had a quarantine in effect almost before "the dust had settled" after the blast
Well, those are just my thoughts =D, i'm kinda a "science guy" so to speak so this makes the most since to me.