Essentially personifying the proverbial Angel and Devil on Cole's shoulders, Kuo is a patriotic NSA agent who harnesses the power of ice, while Nix is a hot-tempered New Marais native who can wield oil and fire. But while the original Infamous often presented users with black-and-white choices, Infamous 2 attempts a more nuanced approach by introducing two new super-powered characters who offer different solutions to each problem. Morality continues to play a part in the storyline and in-game mechanics, as gamers must decide whether Cole should act out of pure altruism, selfishness, or any of the gray areas in between and the choices players make ultimately determine Cole's appearance and powers. Sandbox-style gameplay returns, giving players the freedom to roam the city's slums, swamps, and plantations at will, taking advantage of Cole's parkour-like acrobatic climbing skills, and his ability to 'grind' along power lines and hover through the air on a cushion of electricity. Further complicating matters is the fact that citizens of New Marias are being terrorized by mutated swamp creatures known as The Corrupted, and the city has been placed under martial law by the iron-fisted politician Joseph Bertrand, III, whose militia has been ordered to kill all 'unpure' dwellers, including MacGrath.

Infamous 2 continues the saga of Cole MacGrath as players guide Sucker Punch Productions' electrified superhero to the New Orleans-like city of New Marais in order to enhance his powers in preparation for a battle with a devastating evil known as The Beast.

Infamous 2 hero edition