- Any reference to the physical abuse and bullying that Octavius endured as a child.
- In one of Otto's Pet the Dog moments, he tried to develop a cure for AIDS in order to save an infected ex-girlfriend. He felt devastated when he realized that he failed. His ex eventually died.
- In Superior Spider-Man, circumstances forced Octavius to break up with his girlfriend, Angelina (Stunner). She's devastated, and Octavius also looks unhappy as he leaves.
- When the Hand tries to resurrect Otto using Spider-Man's life-force, Spidey manages to escape forcing Stunner to substitute herself thinking they can cheat the ritual requirement of death as Angelina's Stunner body is only a digital avatar. Instead it fries her brain leaving her comatose, and a revived Octavius is heartbroken cradling her real body.
Tearjerker / Doctor Octopus