2018's Marvel's Spider-Man perfectly encapsulated the essence of what it would be like to save New York City as the Friendly Neighborhood Spider-Man. This included freeing moments like swinging through the city or fighting thugs with the proportionate strength of a spider, as well as the troubles of being unable to pay rent and occasionally disappointing friends and family. However, the best thing about the game was its faithful take on the villains that made them both fun and scary.
The majority of the game primarily focused on Martin Li, Mr. Negative, as the title's main antagonist. However, the background storylines slowly unraveled the relationship between Peter and his mentor Otto Octavius. While most fans knew that he would eventually become the villainous Doc Ock, no one was prepared for his complete heel turn and eventual act that made him Spidey's deadliest adversary.
Following a nearly deadly attack by the Sinister Six, Doc Ock's reveal acted as more of a betrayal to Peter, who looked up to Otto like a mentor and father figure. However, while Pete was busy with Mr. Negative's plans, he failed to notice that Otto's turn to villainy was happening right under his nose. Players were teased with this as he began to work on his prosthetic arms, which were meant to be a solution to Octavius' debilitating disease that would slowly force him to lose control of his body.
Otto's desperation led him to forego the safety precautions for his neural link to the arms, and it ultimately drove him into a state of mania. Now, with revenge on his mind, Octavius was determined to make Norman Osborn pay for when he was shunned from Oscorp. For Doc Ock, this meant releasing a disease called Devil's Breath, which originated at that Osborn's company.
When it was dispersed in Times Square, Devil's Breath had no cure and infected thousands. This act of terrorism put all of New York in a state of chaos. This was coupled with the release of countless Raft inmates that included the Sinister Six. Inadvertently, Ock's decision to infect New York also put May's life at risk, which gave Peter even more motivation to stop his former friend. Eventually, Spider-Man was able to defeat Octavius and synthesize an antidote, but not without major losses.
While Peter saved many, he could not save his Aunt May, a loss that hit harder than the confirmation that Otto knew Peter was Spider-Man even before his villainous reveal. Octavius' turn to villainy was more than a painful truth to Peter, who now understood how little his mentor truly cared. Otto's massive intellect and disregard for human life drove him to terrorism and murder. He felt no remorse. The decision to paint the character in this light solidified him as Peter's deadliest enemy.