Doctor Octopus uses stolen OsCorp tech to invade Ryker's Island to break out Electro, Rhino, Kraven the Hunter and Scorpion then equips them with armor. Doctor Octopus also equips Lizard with armor and another control device. The armored Sinister Six give Spider-Man a hard time until Iron Patriot and the rest of Spider-Man's team arrives. Spider-Man's team fight the other four members, Spider-Man fights Lizard, and Iron Patriot fights Doctor Octopus. The Sinister Six then switch opponents (a thing that Spider-man told his team to do before) but resume fighting the same team members and defeating them. When the armored Sinister Six combine their attacks to take down Iron Patriot, Doctor Octopus plans to inject Spider-Man with the Goblin serum but instead injects Iron Patriot while Spider-Man restored Lizard back to Connors. Thanks to Green Goblin's rampage, Spider-Man defeats half of the Sinister Six. Though Spider-Man has won against the Sinister Six, Green Goblin gets away with Spider-Man's team. After the Sinister Six were defeated, Connors thanks Spider-Man for saving him.
- Doctor Octopus/Dr. Otto Octavius (Leader)
- Electro/Max Dillon
- Kraven the Hunter/Sergei Kravinoff
- Lizard/Dr. Curt Connors (Unwillingly)
- Rhino/Alexander Sytsevich
- Scorpion/Max Gargan
Background in other media =
- In the comics, The second Sinister Six consisted of Doctor Octopus, Vulture, Electro, Mysterio and Sandman and with Hobgoblin replacing Kraven the Hunter.