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I've always read that the character and story are much better in inFAMOUS, and its more fulfilling leveling up and progressing your powers. Where as the character in Prototype has more powers available from the start to quickly pick up and play and wreck havoc on stuff, but he is a less likable character and the game has a weaker story.

Also inFAMOUS gives you the choice to be good or evil while Prototype is just evil.
That said I'll be picking up inFAMOUS on day 1. Prototype will be a rental.
The Uncharted 2 multiplayer beta really pushed me over the edge to buy inFAMOUS.