Alternate Continuity: At the time in which the game came out, it was actually more or less in continuity with the Ultimate Spider-Man comics (and that's also how it was marketed). After some time, however, the comics went in a direction that couldn't support the game's events and a new arc was written that kind of paraphrased the game.
Amusing Injuries: "Don't worry, nothing's broken except my spine... and ribs... and everything."
Artistic License - Geography: The map of New York City is fairly inaccurate, to say the least. A large section of the city is cut off (since it connects very closely to another part of New York) and Queens is depicted as the closest place to the city. Reason behind doing so is understandable though, Peter lives with his Aunt in Queens but operates out of Manhattan, so in order for him to 'go home' and include things such as his school, the two places had to be moved closer. Doesn't stop it confusing non-New Yorkers though.
Badass Normal: The Beetle and Silver Sable—the only two bosses fought by both Spidey and Venom.
In fact, there are cameos from all three of the other Ultimate series (at the time the game was made that is): Johnny Storm from the Fantastic Four, who you can race against, and Nick Fury from the Ultimates.
It's the other way around. The videogame synced very well with the comic at the time it was released. However, scheduling issues pushed the comic adaptation further out. When it finally was adapted from the game, it had to be in Broad Strokes to account for all the other story elements that were already in play.
Car Fu: Venom's weapon of choice. Great against helicopters.
Contractual Boss Immunity/Regret Eating Me: Venom probably shouldn't try to consume anyone made of indestructible blades, anyone made of electricity, anyone who instinctively fires machine guns, or anyone formed of a chaotic spiky symbiote.
Spared by the Adaptation: Venom, the character itself, in the Ultimate comics he barely is a character at all, just a blob which is always hungry and Eddie can't exactly control it; here even without control Venom seems to maintain some intelligence, and Eddie learns how to control it, by the end of the game Venom seems to become much more harmless and lives on, unlike the comics version.
In the comics, even in the story arc this game continues, Venom is not a blob and can even talk like a normal person.
invokedTake That, Scrappy!: In the video game, Venom's tutorial presents you with your first task of absorbing people so that you don't lose health, your first target? A child holding a balloon. In Spider-Man 2, everyone hated the missions of helping kids who constantly lose their balloons.
What Happened to the Mouse?: Unless you buy the special edition, you never learn what Beetle was doing attacking Spider-Man and Venom and what happens to him is never explained. He was collecting samples of superpowered beings for Doctor Doom.
What the Hell, Hero?: Spider-Man calls out Nick Fury (and Silver Sable, mistaking her as his employee) for not keeping Electro in custody.