Successfully complete the game to unlock the hard difficulty setting (enemies at level 50). You can also start a new game with your previous characters at their current experience level.
Play as Xavier
Successfully complete all Dr. missions to unlock Xavier.
Unlock Deadpool
Beat the game.
Unlock Iron Man
Collect homing four homing beacons per act, after four are collected get a piece of Iron Man's armor, in Act 5 after locating beacons save Iron Man.