Whether intentional or not, Spider-Man makes a reference to Sam Raimi's Spider-Man films during the Black Cat chase. When Spider-Man encounters the armored mercenaries on gliders, he remarks that "Green Goblin is so six years ago! The kids are into Venom and Sandman now!". At the time of this game's release, it had been six years since the release of Spider-Man (2002) with the main villain of the film being the Green Goblin. Venom and Sandman are the main villains in Spider-Man 3 (2007), which premiered a year before this game's release.
If Spider-Man goes to the top of the Baxter Building, there are spider-tokens disposed forming a "4". This is a reference to the Fantastic Four who's reside in and use the Baxter Building as their headquarters.
Many billboards with advertisements that appear throughout the game such as signing up for S.H.I.E.L.D, H.Y.D.R.A. and A.I.M.
Dependent on the version of the game, either Venom or Eddie Brock, or neither are responsible for the Symbiote invasion.
There are two buildings of the Daily Bugle, one is similar as in the comics, and the other one, three blocks away is housed in the Flatiron building, as it is in Sam Raimi's Spider-Man movies (Spider-Man (2002), Spider-Man 2 (2004), and Spider-Man 3 (2007)), but the letters in the top of the building are horizontal, as in the comics.