The main character of Prototype 2 is James Heller, a man who blames the deaths of his family on Alex Mercer. After surviving a suicide mission and being transformed by the virus released by Alex Mercer, Heller is looking to kill Mercer, who acts as the game's main antagonist. Mercer's motives are unclear, but unlike the first game he is not committed to stopping the virus, but seems to be spreading it.
After the events of the first game, Manhattan recovered from the initial outbreak and everyone thought that the "Mercer Virus" was eradicated. 14 months after Prototype, Manhattan has been quarantined again, due to a second outbreak, one far worse than the first one, and blocked off from the other boroughs of New York City, which has been renamed New York Zero (NYZ). The boroughs of New York have been divided into three zones, the Red, Yellow, and Green Zone. Each region stands for how affected New York City is by the Blacklight virus. Most boroughs of New York Zero have been infected. The Red Zone is Manhattan, home of Alex Mercer; in it the Blacklight virus grows unhindered. The Yellow Zone is a triage area full of shanty towns and the poor; it is very crowded and while the virus grows there, it is at a minimum and Blackwatch is using the Yellow Zone as a petri dish. The Green Zone is non-infected New York City, except there is a heavy Blackwatch presence. James Heller will have missions in each zone and each mission's difficulty will depend on which zone it takes place in. Blackwatch is credited as occupying and controlling NYZ, but they are said to know that New York actually belongs to Alex Mercer even though the latter is only seen rarely.
Blackwatch is the organization that is responsible for the creation of the virus and are in charge of eradicating it from New York City. Heller's main adversary in Blackwatch is Colonel Rooks. Accompanying Rooks is Dr. Koenig, the main virologist at Gentek. Koenig oversees every major Gentek operation.
James Heller can shapeshift and assume other people’s identities and memories by consuming them. Taking people's identities and shapeshifting into them has become more tactical. Due to Blackwatch's actions in the Yellow Zone, if the player assumes the role of a soldier, people will react to him in a way that they show they want nothing to do with him. To make sure that enemies do not overwhelm the player, Radical has created a dodging system and new, more realistic AI. Heller will be able to use weapons in the game, such as ripping the cannon off a tank and using it against enemies. Heller can also sneak up on unsuspecting human enemies, inject the Blacklight virus in them and create a "BioBomb" out of them to blow up objects, enemies and such. Heller also has improved strength, movement, invulnerability (self-healing and endurance), and has a sonar sense. The sonar includes a new pulse ability that highlights the key features of an environment to make it easier for the player to find someone, instead of looking in a large crowd for a person with an icon above their head. Radical has stated that the powers will be more meaningful, appearing as mutations and upgrades that let players decide how they want to play as Heller.
To give gamers more power in the game, the developers have added tendrils. Tendrils sprout from Heller's arm and can be used for a variety of purposes. Players can use tendrils to smash objects into other objects, such as a car into a tank, utilising the 'Black Hole' attack. Players will be able to dismember enemies, a force that will become more useful as the game progresses. There are many more ways to kill enemies, ranging from throwing a car at a group of Blackwatch soldiers, hacking off a mutant's head or using powers. Consuming has not changed since the original Prototype, with the exception of some enemies, which are consumed upon grabbing them (e.g. Supersoldiers, Brawlers). It has also been announced that Heller can now control a pack of Brawlers (similar to Prototype's Hunters) to attack anything he desires (note: this power is limited to main variant of Brawler). Heller will no longer find 'Events' throughout NYZ, instead starting side-missions by hacking into Blacknet. Hacking onto Blacknet, Blackwatch's system that details military operations and the three areas of NYZ, Heller chooses from a small list of missions at each terminal. Blacknet will allow Heller to find operations that he can disrupt or take control of for his own purposes and find important people that will allow him to learn more about what he has become because of the Blacklight virus. It will also help him find out more about Alex Mercer and what his connections are to his family's deaths. The missions that are selectable can be sidequests or extensions to the main quest that tell Heller more about the Blacklight virus.
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