[1] In Prototype, players control an amnesiac shapeshifter named Alex Mercer as he attempts to stop an outbreak of a virus called Blacklight in Manhattan, which mutates individuals into powerful, violent monsters.

Alex also attempts to uncover his mysterious past while coming into conflict with both the US military and a black operations force called Blackwatch.

Outside of the main story, players can freely explore the game's open world and engage in several different side activities.

Even small jumps are enough for Alex to dent the ground beneath him, and falls from sufficient heights will create shockwaves at the point of impact which will kill most humans nearby and send objects as large as cars flying.

The Military consist of ordinary soldiers which are usually not a major threat, but they are capable of operating weaponry that is extremely dangerous to Alex, such as tanks and heavily armed helicopters.

"Alex" Mercer (voiced by Barry Pepper), a shapeshifter suffering from amnesia, causing him to forget his previous life, including how he obtained his powers.

As he attempts to uncover his past and stop an outbreak of a virus called Blacklight, which has overrun Manhattan, Alex comes into conflict with two factions: the United States Marine Corps and Blackwatch, a Fort Detrick special forces unit dedicated to combating biological warfare; and the Infected, people infected by the Blacklight virus, which turns them into violent monsters.

The main antagonist is Robert Cross (Jeff Pierce), also known by his codename, "The Specialist", a Blackwatch officer tasked with containing Alex.

Supporting characters include Alex's sister Dana Mercer (Lake Bell); Dr. Bradley Ragland (Phil LaMarr), who helps Alex throughout the game; Alex's ex-girlfriend Karen Parker (Vanessa Marshall); Dr. Raymond McMullen (Paul Guilfoyle), founder and head researcher of bio-research company Gentek; General Peter Randall (Gordon Clapp), the head of Blackwatch; Randall's second-in-command, Ian Taggart (Richard McGonagle); and Elizabeth Greene (Kari Wahlgren), also known as "The Mother", a former test subject that hosts the Blacklight virus.

Alex Mercer wakes up in a morgue in the basement of Gentek, a genetic engineering company based in Manhattan, scaring away a pair of scientists that were about to perform an autopsy.

With no memory of his previous life, Alex decides to find and consume those related to the conspiracy in order to uncover the truth, quickly bringing him into conflict with the US Military and Blackwatch, a black ops unit trying to contain the Blacklight virus which is overrunning Manhattan.

Dana directs Alex to Karen Parker, his ex-girlfriend, who agrees to aid him in stopping the Blacklight outbreak, asking him to bring her samples of the virus.

An anomaly in her body's biology accepted the virus, rewriting her genetic code and causing her to take control of the infected town, becoming hostile in the process.

Eventually pinned down by Blackwatch in Penn Station, Alex, in a final act of desperation and vengeance, shattered the vial containing the Blacklight, releasing the virus before being gunned down.

The virus entered Alex's bloodstream through the bullet holes and repaired his body at the cellular level, giving him his powers in the process.

The contact and Alex pump a new "Bloodtox" biological agent underground in order to drive the virus above ground where it can be fought directly, causing Greene to emerge, encased in a towering monstrosity.

A US Senator is heard telling the media that the events in Manhattan were a case of nuclear and biological terrorism, and promises retribution upon those responsible.

[13] The comic book miniseries functions as a prequel to the game, revealing more details about the Blacklight outbreak and characters such as Elizabeth Greene.

[41] GameSpot praised the game for its "intriguing storyline and protagonist" and "massive arsenal of moves and abilities", but criticized it for its "occasionally fiddly controls" and "dull scenery".

[20][19] The Escapist said the Xbox 360 version was a perfect "summer fling," praising the combat and movement systems as well as the unique mechanic of the Web of Intrigue.

Club gave the same console version an "A−" ranking, calling the movement style "exhilarating" and saying it was a "mature, science-fiction superhero fantasy that somehow makes players feel simultaneously powerful and vulnerable.

The pure adrenaline-boosting entertainment value of the finished product is enough to push most visual and gameplay niggles far enough into the background so as to eradicate them as concerns in all but the most snobbish of gamers.

"[44] However, Teletext GameCentral gave it five out of ten, concluding, "The initial feelings of power and freedom hide another badly designed and unimaginative superhero sim.

[46] Prototype was released two weeks after Sucker Punch Productions' Infamous, a game with many similar concepts including a character with superpowers, and a large open world environment that can be traveled by climbing up buildings and gliding about the city.

[52] To decide which one was better, he jokingly stated that he'd award the best game to the team which created the best picture of the other main character wearing "a woman's bra".

[53] A review on GameSpot.com says: "[Mercer is an] incredibly fun character to play as in a game that also counts an intriguing story, varied missions, and some memorable boss battles among its features.

The game follows a new protagonist, former U.S. Marine Sergeant James Heller, as he pursues vengeance on Alex Mercer, who serves as the main antagonist.