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- The PC/Mac version is much more linear and lacking the web mechanics of the console versions. The game also features small spaces, not a Free-Roaming Manhattan as the other versions.
- In the PC/Mac version of Spider-Man 2 some computers in the OsCorp and FNB levels show the Spider-Man 2 game.
- In the PlayStation 2 version, a sign on one of the buildings said "Tobey's Toy Store," a nod to actor Tobey Maguire.
- In the PSP version, the player can only swing in the sky, much like the first 3D Spider-Man games.
- The DS and PSP version concerns the escape of The Vulture.
- In the PC/Mac version, Spiderman shoots web at web targets; in the GameCube, PlayStation 2, and Xbox, Spiderman shoots a web at an actual building.