Alternate Continuity: The game is more of an entire reimagination of Ultimate Spider-Man than a real adaptation. For instance, the take on Venom and Spidey is completely different: Venom in particular is quite sympathetic and his fate is much better (for him) than in the comics. At the time in which it came out, it was actually more or less in continuity (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.
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.