- Otto getting electrocuted.
- The way Rosalie is killed. Getting impaled by hundreds of glass shards that you can see flying right at you and being able to do nothing but scream...
- Octavius' mechanical tentacles killing the doctors. See for yourself.
- The scariest part? Otto was unconscious. His tentacles did that all on their own. Imagine waking up after a horrible accident, only to find yourself in a hospital with everyone in the room dead. You begin to hear a voice. Four, in fact, each one of them telling you to do horrible things.
- Ock kidnapping MJ. That smile just before he picks her up...
Doc Ock: Find him. Or I'll peel the flesh off her bones.
- The loud stomps of Doc Ock as he climbs up to Harry's balcony to confront him. Roger Ebert referred to the tentacles scaling a building sounding like "the drums of hell".
- Harry hearing the Goblin laughter just before he starts hallucinating Norman's reflection in the mirror.
- "AVENGE ME!!"
- From the PC version of the game, New York is turned into floating islands, courtesy of Mysterio. In the first part, the floating islands are only several hundreds metres or so above the ground. In the second part, the floating islands are located very close with the earth's atmosphere, where many meteors hit and the ground can be barely seen. In the third part, the floating islands are in outer space.