Which Spider-Man villain founded the Sinister Six?

Doctor Octopus founded the Sinister Six.

After repeated clashes with Spider-Man, Doctor Octopus—whose real name is Otto Octavius—organized a team of five other villains to defeat their common enemy. The original lineup included Vulture, Sandman, Electro, Mysterio, and Kraven the Hunter, with Doctor Octopus acting as leader.

The Sinister Six first appeared in The Amazing Spider-Man Annual #1 in October 1964. In their debut story, they kidnapped Aunt May and Daily Bugle secretary Betty Brant, then arranged for Spider-Man to face each villain separately. Spider-Man defeated them one by one, exposing the weakness of their rivalry and lack of teamwork.

Green Goblin and Kingpin are major Spider-Man antagonists, but neither founded the original Sinister Six. Mysterio was one of the founding members, not the organizer. The team has since had many changing lineups, but Doctor Octopus remains its defining founder and frequent leader.