The role of Harry Osborn, voiced by Scott Porter in Marvel's Spider-Man, was recast in the game's sequel, with Graham Phillips now voicing the character. In a now-deleted tweet, Porter revealed that the reason he was recast was due to Insomniac's decision to go "photo real" with the character's graphics in the sequel, which left him out of the role due to the drastic age gap between the actor and the character.

The decision to go "photo real" was likely for the same reasons that Insomniac changed Peter Parker's face for the remastered version of the first game in 2020, and later games. The team gave a brand new face for Peter Parker, apparently in order to "bring the best performances to players," Insomniac said at the time.