|Members|| Doctor Octopus|
Kraven the Hunter
|Former Members|| Beetle|
When Spider-Man arrived, they attacked him and Doctor Octopus transformed Connors back into the Lizard. All six attacked him alone, attempting to unmask him. He escaped outside the lab and called his team, where White Tiger, Power Man, Iron Fist, and Nova arrived and they defeated their opponents. Spider-Man got Connors to resist Octavius' control, smashed his control device, and then unplugging Otto's four arms with the Lizard knocked out.
However, the Lizard soon woke up and escaped into the sewers and Spider-Man tried to save him, but the Lizard said he wouldn't stop failing. The other five members of the Sinister Six were then locked away in S.H.I.E.L.D.'s new headquarters.
Later, Doctor Octopus uses stolen OsCorp Industries technology to invade Ryker's Island to break out Electro, Rhino, Kraven, and Scorpion. He then equipped them with armor. Doctor Octopus also equipped 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 fought the other four members. Spider-Man fought Lizard while Iron Patriot fought Doctor Octopus. When the armored Sinister Six combined their attacks to take down Iron Patriot, Doctor Octopus planned to inject Spider-Man with the Goblin serum but instead injects Iron Patriot. Spider-Man restored Lizard back to Connors. Thanks to Green Goblin's rampage, Spider-Man defeated half of the Sinister Six. Though Spider-Man had won against the Sinister Six, Green Goblin got away with Spider-Man's team. After the Sinister Six were defeated, Connors thanked Spider-Man for saving him.
This is the second time their comic book name is used. It is also the second time that Doctor Octopus formed the group, as he originally did in the comics.
In the Comics
Doctor Doom, Lizard, and Green Goblin were asked to form the original Six but all refused. Doctor Doom wanted to spend his efforts on the Fantastic Four. Green Goblin felt he could do defeat Spider-Man on his own. Connors had no reason to stop Spider-Man when not the Lizard.