From the videos I've seen Prototype looks more like a balls to the wall action games where you're basically running around like a madman destroying anything and everything in your path. InFamous looked more focused and not so all over the place. There's also the climbing and running mechanics in InFamous that kind of throws back to Sucker Punch's Sly Cooper and I've not seen anything like that from Prototype.
Also, isn't there an alignment system in InFamous that brings you from Hero to Anti-Hero, does Prototype have that?
I also know in Prototype your power is of shape shifting and in InFamous it's electric-based powers. Also, I know in Prototype you can hijack vehicles and stuff like GTA and I've not seen any of that in InFamous stuff I've seen
I'm no expert on either, just going by what I've seen from videos and screens. They both definitely are the same concept (free-roaming, open-ended superhero experience), but the actual gameplay looks pretty different from what I've seen. Don't know about storywise, though