Among readers and fans, Spider-Man is Marvel's most popular superhero. In-universe though, the wall-crawler isn't always popular, and has plenty of enemies. Of the many rogues galleries in comics, his is one of the largest. Beyond that, he's often libelously branded as a menace by the media.
With so many people out to get him, Peter Parker's life being so stressful isn't a surprise. Of these many enemies, there are the most frequent thorns in Spider-Man's side. Those who he most frequently foils the evil schemes of, and who have the most simmering hatred for him.
10 J. Jonah Jameson Has Made A Career Slandering Spider-Man
J. Jonah Jameson is far from Spider-Man's most dangerous adversary, but there's a case to be made that he is the most consistent. Since he debuted in The Amazing Spider-Man #1, the penny-pinching, perpetually-irate EIC of the Daily Bugle has dragged Spider-Man's public reputation through the mud.
Worse, he's even funded super-villains like The Scorpion and the robotic Spider-Slayer. Jameson's motive varies. From simple sensationalism, a mistrust of masked men, to jealously of how Spider-Man steal coverage from his astronaut son, John.
9 The Jackal Hated Spider-Man For Gwen Stacy's Death
The Jackal isn't as prolific as some of Spider-Man's other foes, but his machinations have led to some of the most painful times in Peter's life. The villain was originally Professor Miles Warren, a biology professor who taught Peter Parker and Gwen Stacy at Empire State University.
Infatuated with the much younger Gwen, Warren was distraught after her death and blamed Spider-Man for failing to save her life. Becoming the Jackal, Warren put his scientific talents to use, creating clones of Spider-Man and Gwen, kicking off the Clone Saga.
8 Electro Would Love To Fry Spider-Man
In The Amazing Spider-Man #9, an accident turned turned Max Dillon into the super-powered Electro. Still a petty and not particularly bright man, Electro turned to crime and ran afoul of Spider-Man. Adaptations try to reinvent Electro's backstory to make him more sympathetic. In the comics, Electro is a violent thug in search of a big pay day and more power. Spider-Man always prevents him from achieving both, so Electro naturally holds a serious grudge against the hero.
7 The Vulture Is One Of Spider-Man's Oldest Enemies
Adrian Toomes, aka the Vulture, was one of the first super-villains Spider-Man ever faced, all the way back in The Amazing Spider-Man #2. He could even qualify as Spider-Man's first recurring nemesis, considering he swiftly returned in Amazing Spider-Man #7 after his first defeat. The two have a lot of history, most of it consisting of Spider-Man defeating and humiliating the Vulture. Toomes has a lot of hatred for the wall-crawler. This hatred burns hotter each time Spider-Man bests him.
6 Spider-Man Was The First Superhero Who Inconvenienced The Kingpin
Wilson Fisk has a more personal enmity with Daredevil, but his original superhero rival was Spider-Man. The Kingpin Of Crime first appeared in The Amazing Spider-Man #50. Spider-Man No More! sees Peter briefly quit being Spider-Man, and the Kingpin took advantage of the vacuum to amp up his operations.
After Peter returned, the Kingpin and his enforcers were the first foes he faced. Even as Kingpin has become more associated with Daredevil, his hatred for Spider-Man endures. In Ultimate Spider-Man, Kingpin even purchased the merchandising rights for Spider-Man to get under his heroic rival's skin.
5 Mysterio Is Filled With Resentment, Especially Towards Spider-Man
Quentin Beck was a special effects engineer frustrated by his inability to break out in front of the camera. This resentment plays into Beck's modus operandi as the super-villain, Mysterio. In The Amazing Spider-Man #13, Mysterio tried to usurp Spider-Man's status as a superhero, framing Spider-Man for crimes he had committed.
Once the ruse was unveiled, Mysterio became a full-time member of Spider-Man's rogues gallery. Frustrated by Spider-Man's consistent victories and his frequent mockery, Mysterio is one of his most hateful enemies.
4 Scorpion Was Made To Be Better Than Spider-Man
J. Jonah Jameson's worst sin against Spider-Man happened in The Amazing Spider-Man #19-20. Jameson hired PI Mac Gargan to find Spider-Man's true identity. When he failed, Jameson used Gargan as a test subject for an experiment to create an anti-Spider-Man figure. The resulting experiment turned Gargan into the Scorpion, an animal that's the natural predator of a Spider-Man. Gargan himself is one of the most vile and sadistic of Spider-Man's foes, sadism which escalated when he bonded with the Venom symbiote.
3 The Venom Symbiote Is Spider-Man's Scorned Ex-Partner
Hell hath no fury like a Symbiote scorned. The Symbiote, which became Venom, was exiled from its home planet of Klyntar and eventually found its first love in the form of Spider-Man. Venom craved a permanent bond with a host and Peter's enhanced physiology made him perfect.
When the Symbiote started hijacking Peter's body while he slept and negatively influenced his behavior, he rejected it. Spurned, Venom has since bonded with a string of hosts. Most famously, Venom hosted Eddie Brock, another fellow Spider-Man hater. Oftentimes they were in hopes of getting revenge on Spider-Man.
2 Doctor Octopus Is One Of Spider-Man's Greatest Enemies
Doctor Octopus first appeared in The Amazing Spider-Man #3 and was an immediate mirror to the hero. Like Peter, Otto Octavius' powers were the result of science gone wrong (albeit robotics rather than biology). Doc Ock was also the first villain to give Spider-Man a true run for his money.
Though he faces stiff competition for the title of Spider-Man's arch-enemy, Octavius is Peter's most enduring. He was the founder of the Sinister Six. In Superior Spider-Man, he stole Peter's life by body-swapping with him. Though Otto emerged from the experience more heroic, it took him literally getting inside Peter's head for Otto to feel any empathy.
1 Norman Osborn Loathes Spider-Man, Yet Covets Peter Parker As An Heir
The Green Goblin, specifically Norman Osborn, is Spider-Man's arch-enemy. Norman barely edges out Doc Ock and Venom for the dubious honor. Osborn is uniquely sadistic and ingenious among Peter's enemies. Osborn's murder of Gwen Stacy is still the deepest wound a super-villain has inflicted on Spider-Man.
As much as Norman detests Spider-Man for constant interference in his plans, he does admire Peter Parker. Norman sees qualities in Peter - intelligence, grit, ambition, and a buried ruthlessness - that he shares and his own son, Harry, lacks. This means Norman hates Peter all the more when the young hero rejects his tutelage.