Although Spider-Man: Web of Shadows shares some features as previous Spider-Man games there are also many differences including no movie connection for starters.
A flashback in the beginning reveals how a fight with Venom causes some symbiote to attach to Spider-Man giving him greater strength. Spider-Man then meets Luke Cage who helps train him to defeat the city gangs. During an attempt to save some gang leaders from assassins, Spider-Man is attacked by residents who are controlled by symbiote. The symbiote substance terrorizes the city as it spreads and attaches to innocent citizens. Spider-Man begins a quest to save New York City.