inFAMOUS is one of my favorite new IPs, and the first one was, and probably still is one of my favorite games this generation. inFAMOUS 2 expanded on the gameplay by adding new powers, characters and new environments. There is however one huge difference between the games.
In inFAMOUS, your choices affect your powers, but have very minor influences on the ending. So when you do get to the end of the game, whether good or evil, the ending is essentially the same. In inFAMOUS 2, Sucker Punch created a huge difference between the endings depending on your karmic choice at the end.
I'm trying to keep this article spoiler-free, but the evil ending in inFAMOUS 2 is completely different to the good ending. This suggests that either there won't be a third game in the series, which would be a huge shame, or it will be a completely different game. There is a third option, and that is to ignore one of the endings, and base the third game on one of the endings only. For those who've not played the game, the only spoiler-free example I can think of is giving an analogy.
In I Am Legend, the original ending is where Will Smith passes the antivirus to the woman, and blows himself up with the zombie-like creatures. Subsequently, a sequel (not a prequel) to this film would not star Will Smith, because he's been removed from the equation. On the other hand, the alternative ending saw Will Smith survive, but allow the zombie-like creatures to take back their companion. With this ending, an I Am Legend 2 would work.
inFAMOUS 2 gives you a similar predicament, but the endings are so different, that it would require you to create 2 completely different games for inFAMOUS 3 to work. For those who've not finished the game on evil yet, I highly recommend you do, because the ending is very good, and very different from the good ending. However, as I said, it looks like we might not see an inFAMOUS 3, but I hope to God we do.