There were plans to include a multiplayer mode in the game, but the idea was dropped due to time constraints after the developers were riddled with set backs during development.

The Web of Intrigue states that Karen Parker was born in January, 1976, making her 32 years of age during the events of the game (which takes place in 2008). However, the game's official website states that Karen is actually 27 years of age.

It is believed that the Web node was an early development script that wasn't changed before the game's final release in 2009. Karen's official date of birth has been confirmed as 1981.

In June 2009, game journalist Ben "Yahtzee" Croshaw uploaded video reviews of the games Infamous and Prototype as part of his employer The Escapist's web series Zero Punctuation. In his review of Prototype, he compared both games for having similar premises and being of similar quality (each game released a few weeks apart), but to determine which was the best, he jokingly challenged both games' developers to submit an image of their competitor's protagonists wearing a woman's bra. The developers unexpectedly took the challenge seriously and one-upped it the following week, with Sucker Punch Productions producing a portrait of a gender-swapped Alex Mercer, and Radical Entertainment producing an image of Cole MacGrath as a drag queen in lingerie. Croshaw followed up by reviewing the two images, noting that they had similarities even beyond the prompt, including unicorns and rainbows: