9. Doctor Octopus
A four-issue miniseries titled Space: Punisher takes place in the reality designated Earth-12091, and it's very different from the Marvel Universe of Earth-616. In this reality, the Punisher operates in space, as the name implies, and his primary antagonist is a group called the Six-Fingered Hand.
The group consisted of Brood Queen, Ultron, Doctor Octopus, Green Goblin, Magneto, and the Red Skull, and they were responsible for the death of Castle's family. Frank learned from the Leader that he was hired by Doc Ock, which infuriated him, leading to a quick capture of the villain.
He strapped the Doc to the front of his spaceship and gave him a tour of the galaxy, but doing so cost Ock the use of his vocal cords. He survived the vacuum of space due to the fact that he could go without oxygen for long periods due to being half-man/half-octopus.
Frank landed his ship and saw the damage he caused, but when Ock couldn't even whisper the information Frank was hoping to learn from him, he decided to put him out of his misery. A single shot to the face at point-blank range with a pistol turned Doc Ock's head into a cloud of bloody mist.