Which Villain Has Ruined Spider-Man’s Life The Most?

In many ways, Norman Osborn was Peter Parker’s first, and worst, arch-nemesis. After becoming the first supervillain to truly learn the wallcrawler’s secret identity, Osborn infamously kidnapped the young Gwen Stacy and threw her from a bridge, resulting in her tragic demise. And, as if that weren’t awful enough already, it would later be revealed that Osborn had also coerced Stacy into an affair shortly before the kidnapping, resulting in two secret superpowered children who would go on to plague Spider-Man for years.

But the OG Goblin wasn’t done there. Though he was thought to be deceased via self-inflicted glider-impalement, Osborn moved into the shadows and began orchestrating the events of the "Clone Saga," a lengthy story arc that saw Parker convinced that both that his Aunt May had passed and that he himself was a clone. And, as if that weren't awful enough, then Osborn ended Ben Reilly, Spidey's clone "brother," with his glider.

Osborn later reemerged as a public figure, sans Goblin gear, and rose to enough prominence to take over S.H.I.E.L.D. for a time, ensuring that Spidey had to live for a few years with his worst enemy effectively in charge of the Marvel Universe. Then, it was back to the goblin life for Osborn, who partnered up with the Carnage symbiote and took out Parker’s dear friend and former best man, Flash Thompson. 

Early on in their respective careers, Otto Octavius established himself as a very personal threat to Spider-Man. He was the first villain to unmask Peter Parker publicly - though it was all chalked up as a misunderstanding - and a battle between the two resulted in the accidental demise of George Stacy, the father of Peter’s girlfriend Gwen. This drove an enormous wedge between Peter and Gwen that would not be fully resolved before her own untimely demise.

Then, Doctor Octopus founded the Sinister Six and became more of a team player, but that didn’t mean he was done being a singular menace to the webslinger. After a couple of unsuccessful ploys, including an attempted marriage to Aunt May and a scheme in which he held the entire world hostage, Doc Ock received a terminal diagnosis and set about hatching his greatest crime yet. Using mind-swapping technology, he stole Spidey’s body and then his life, becoming the Superior Spider-Man while Parker perished in Ock’s original body. Eventually, Ock would learn some important lessons and give the body back, but only after wearing it around for a year and seriously sullying Spidey’s hard-earned reputation. 

Though Wilson Fisk is a menace to any and all doers-of-good in New York City, Spider-Man included, he’s usually saved his most heinous acts for Daredevil. But that doesn’t mean Fisk hasn’t clashed with Peter Parker regularly, though it’s rarely very personal - except for that one time it became very, very personal.

During the events of Civil War, Iron Man convinced Spidey to unmask publicly - a decision that would immediately produce major consequences. Though he was incarcerated at the time, Fisk hired an assassin and gave them specific instructions to avoid Parker’s Spider-Sense. Tragedy struck, however, when the bullet intended for the webslinger found his Aunt May instead.

Spider-Man would spend the next several days searching desperately for a way to save his aunt’s life, ultimately making a deal with Mephisto to restore her health - at the cost of his marriage to Mary Jane. He did also deliver a horrific and vengeful beating to Fisk in retaliation for his actions - but for a person as obsessed with responsibility as Spidey is, this also proved a traumatic experience. 

Despite being one of Spider-Man’s most prominent rivals for decades, the classic version of Venom - as in, the Venom symbiote when paired with Eddie Brock - hasn’t really done all that much to harm Peter Parker directly. At first, the composite being’s mutual hatred of Parker resulted in a series of stalkings and assaults - including the brutal beating of Spidey’s one-time love interest, Black Cat, and the terrorizing of poor Aunt May - but by the time Carnage arrived on the scene, Spidey and Venom were more or less uneasy allies.

More damaging to the wallcrawler, however, has been what Venom represents. Typically, Parker has done a remarkable job of keeping his secret identity under wraps, and he’s got his Spider-Sense to warn him of any threats that still manage to hit close to home. But Spider-Sense doesn’t work on Venom, and Venom inherently knows all of Spidey’s secrets. The moment when Parker swung into his own apartment, only to find Venom holding his wife Mary Jane hostage, was probably the first true surprise he experienced in his webslinging career, and it wasn’t a pleasant one. Thus, Venom robbed Spider-Man of his sense of security.

When the Carnage symbiote, birthed from Venom, bonded with notorious serial killer Cletus Kasady, the result was a nigh-unstoppable villain that made a habit of going on violent sprees - but never really targeted Spider-Man specifically. In fact, the combined character of Carnage has since become much more of a rival to Venom than he is to Spidey, though the symbiote itself has continued to plague the wallcrawler’s life.

At one point, Norman Osborn got his hands on the alien goo in question, bonding with it to become the Red Goblin. With greatly enhanced power and madness, Osborn then waged a personal war on Peter Parker. Not only were several of Parker’s loved ones placed in mortal peril, but his former best man, Flash Thompson - himself having become a symbiote-wielding hero - also perished in battle with the Red Goblin, though not before learning that his childhood hero and close friend were one and the same. 

Mephisto is the Marvel Universe’s primary stand-in for the biblical Satan, and as such, he’s sort of a villain to all. Of course, Mephisto rarely makes a direct strike against anyone, preferring instead to offer them loaded deals - devil’s bargains - that always come with a catch, ensuring that he comes out on top and whoever he made the deal with suffers.

Few, however, have suffered more from Mephisto’s machinations than Peter Parker. With his Aunt May hanging on to life by a thread after taking an assassin’s bullet, Peter and his wife Mary Jane were approached by the demon with an offer they couldn’t refuse; allow him to retroactively wipe their marriage from existence, and he would restore May to perfect health. Peter and Mary Jane reluctantly agreed, and it was only after the metaphorical ink had dried than Mephisto introduced them to a young, redheaded girl - the daughter they would have had if their marriage had remained intact, who would now cease to even come into existence.

Thankfully, Peter and Mary Jane’s love proved more powerful than even the devil, and they’ve since gotten back together after several years apart.