The story begins with the arrest of Wilson Fisk (Kingpin). While Peter believes this will bring peace, Fisk warns that his absence will only create a power vacuum for worse threats.
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Follows the return of Peter's ex-girlfriend, Black Cat (Felicia Hardy), who is being blackmailed by the Maggia crime families. The story begins with the arrest of Wilson Fisk (Kingpin)
Octavius orchestrates a massive breakout at the Raft, forming the Sinister Six (Electro, Vulture, Rhino, Scorpion, Mister Negative, and himself). He releases a deadly biological weapon called "Devil's Breath" —originally a failed cure for Norman Osborn's son, Harry—across New York City. Follows the return of Peter's ex-girlfriend, Black Cat
Peter works as a lab assistant for Dr. Otto Octavius , a brilliant scientist developing advanced prosthetic limbs. After their funding is cut by Mayor Norman Osborn, Octavius becomes obsessed with perfecting his neural interface, which eventually warps his mind and turns him into the vengeful Doctor Octopus .
Peter retrieves the antiserum but faces a devastating choice: use it to save his dying Aunt May, who was infected by the virus, or use the entire dose to mass-produce a cure for the city. Encouraged by May herself—who reveals she has known he is Spider-Man for a long time—Peter chooses to save the city, and May passes away. The City That Never Sleeps (DLC Story)
Focuses on the brutal mob boss Hammerhead , who uses stolen Silver Sable technology to wage war on the other crime families.