Superbeasto and Suzy X trick Dr. Satan into divorcing his wife, Velvet. This (combined with several other actions) causes Dr. Satan to revert to his mortal form, and he is beaten to a pulp by Superbeasto. In the end, Superbeasto is a star again, Suzy X continues to turn Murray on, and Velvet is shacked up with Otto.
El Superbeasto (voiced by Tom Papa) was a former celebrity who has fallen from grace, and now makes his living by starring in cheap porn. His sister, Suzy X (voiced by Sheri Moon Zombie) is still a kick-ass action hero and is assisted by her robot Murray, who has a huge crush on her. She is on a mission to destroy Hitler's still living head, confronting a horde of Nazi zombies throughout the film.
Dr. Satan (voiced by Paul Giamatti) is a former geek who went to high school with Superbeasto and Suzy. He is now a maniacal scientist who is assisted by his intelligent giant ape assistant, Otto, and his elderly elevator man Lenny. Having built spy cameras throughout the city to peep on girls, he notices that famed stripper Velvet von Black (voiced by Rosario Dawson) has the 666 mark on her butt. If he marries her, he will gain the powers of the actual devil. Otto is sent out to abduct Velvet. Superbeasto, having witnessed the kidnapping, vows to rescue her (believing Velvet will sleep with him if he succeeds).
Superbeasto, Suzy and Murray set off on the rescue mission. Along the way, Superbeasto begins enjoying his adventuring ways and is soon motivated by a desire to restore his former status as a famous crime fighter. Before Superbeasto and Suzy can complete the mission, Dr. Satan manages to successfully woo Velvet with his money and power. The two tie the knot and Dr. Satan becomes an all-powerful giant, easily defeating Suzy and Superbeasto before going on a rampage.
Dr. Satan eventually decides that he wants Suzy to be his partner. This results in Velvet getting into a cat fight with Suzy, as Velvet believes Suzy returns Dr. Satan's affections. Suzy emerges victorious from the battle, and Dr. Satan steps on Velvet, claiming their marriage is over. Because Dr. Satan derived his powers from his marriage, he begins to weaken. Using info in a book on satanic rituals, Superbeasto is able to perform several other actions that cause Dr. Satan to fully lose his powers. Dr. Satan, a scrawny mortal once again, is then beaten into a bloody pulp by Superbeasto.
In the end, we see that Suzy continues to tantalize Murray sexually, Superbeasto has restored his acclaim, and Velvet (who survived being crushed) has shacked up with Otto, after discovering how to activate his animal nature on command.
Two post credit scenes. The first is another musical piece featuring most of the background characters. The second shows that Lenny is actually a young, busty, woman in disguise.
Thanks Evan B!