There are tooooooo many differences and a few similarities
Gameplay is way different.
-You can consume people in Prototype.
-You can use weapons and vehicles (APC's, two types of tanks and two types of helicopters) and call in artillery strikes as a commander. Cole can't use vehicles or weapons.
-Your attacks are melee based mostly, while Cole's abilities are electricity-based. His melee attacks are limited to a few punches and kicks.
-You have special attacks.
-The gameplay is fast paced, the camera is way back to reflect the large scale action.
-In Prototype there is a three-way war going on between you, the Infected and the military, while Infamous doesn't have as many clashes between the various gangs.
Story is different.
-Conspiracy versus large explosion and decimated city.
-You complete the story by absorbing people and their memories, while in Infamous you progress through main missions and comic book style cutscenes.
-There is an Infection, the military and zombie-like creatures, while Infamous has gangs.
Characters:
-Alex is an anti-hero, Cole can be either a villain or a superhero.
-Alex has had very bad things done to him, but also does very bad things, which is why he's in the grey space that he is.
-Alex has total amnesia, while Cole just can't remember the events concerning the blast.
Presentation is different:
-The graphics for Infamous are slightly better than Prototype's.
-There is more detail to Empire City and its inhabitants.
-Infamous is on a small scale, while there are around 200 things on screen at any given moment in Prototype (80-100enemies and 100 vehicles).
-Empire City is quite grey to contrast with the electricity Cole uses, while Prototype's New York is a little more colourful.
-Empire City doesn't change as drastically as Prototype as you play. However, if you are evil/good then it changes accordingly. In Prototype buildings become Hives (bases) for the Infection and the military set up more bases. The screen takes on a normal/red/greenish-greyish tinge accordingly.
They are similar in the fact that both characters have superpowers, both cities are quarantined and both have open-worlds, but all the similarities are really superficial.