Ultron, a genocidal robot who has wiped out an entire nation on his own. Massively on his own, in fact; on that occasion, he turned himself into an army. And after he had killed everyone in the country, he turned their corpses into cybernetic combat drones to fight the heroes.
Later, he tried to pull the same stunt again, only this time he did it with a galaxy. He also cyber-enslaved a slew of cosmic superheroes — and villains, including the Space Knights of Galador, Gamora (the adopted daughter of Thanos), Drax the Destroyer, Xemnu the Titan, Shatterax, Ronan the Accuser, Nova-Prime and the Super-Adaptoid, several of which qualify as Hero Killers in their own right.
And later, he returned in "Avengers" in such a way that the heroes - the most powerful hero team in the world, mind — basically were "Oh, no... not again!"
In The Korvac Saga, Korvac slaughters most of the Avengers and Guardians of the Galaxy without mercy, though he resurrects them all before he dies.
At the time of publication, it was intended by one of the final arcs of Avengers West Coast that Mephisto be one was he killed Mockingbird as a "Fuck you" to the Avengers — then Secret Invasion (2008) happened, which retconned that it was a Skrull who'd kidnapped and impersonated Mockingbird that Mephisto had killled and the real Bobbi Morse was alive and well.
In The Avengers (Jonathan Hickman), The Beyonders are revealed to be the ultimate cause of the incursion, which eventually lead to the destruction of the multiverse and nearly every hero in it.
Captain America: Crossbones is one for the Badass Normal set, having ratcheted up a fair bodycount over the course of his career. He's also the one who fired the shot that killed Cap at the end of Civil War firmly cementing his reputation as one of these.
Captain Britain: The Fury is a powerful robot created by Mad Jim Jaspers to destroy all superheroes, the Fury's adaptive abilities and self repairing mechanisms made it so powerful that it wiped out all superheroes in it's home dimension of Earth-238.
Captain Marvel: Made of Explodium hitman Nitro is notable because he's a low-level C-lister who doesn't even have a nemesis. Yet he is the man who cause The Death of Captain Marvelnote in his debut, no less, though Mar-Vell's death was only a side-effect as the tank containing the gas that ultimately caused Mar-Vell's death sprung a leak as a result of Nitro trying to escape using his explosive powers and it took time for the gas's effects to kill Mar-Vell and caused the events of Civil War by killing most of the New Warriors. Both of these are major events, and in a world where Death Is Cheap, Mar-Vell and Microbe's have stuck.
The Eternals: The Celestials scare the crap out of everyone whenever they show up. Fortunately, they don't go around eating planets left and right. Unfortunately, they have a nasty habit of "judging" worlds they have seeded life on (which is most of them), and executing them if they don't like what they see. Yes, they execute entire planets.
Hulk (2008) sees longtime supporting character S.H.I.E.L.D. agent, and Hulkbuster member Clay Quartermain murdered. It was initially believed to have have by the Red Hulk to keep quiet about his identity. While this is true, it's ultimately revealed that during Fall of the Hulks that General "Thunderbolt" Ross, who's the Red Hulk, wasn't the one who killed him himself, but rather Doc Samson, under the influence of the "Samson" persona.
Spider-Girl: Roderick Kingsley, the original Hobgoblin, becomes this after coming out of retirement. He effortlessly beats down Spider-Girl and her allies with minimal help, kills the Venom symbiote, wrecks Black Tarantula's organisation, and gets away.
Norman Osborn's most well-known murder was that of Gwen Stacy, but he has nearly killed a few super-powered adversaries and did kill Ben Reilly, Peter's clone. He then ups the ante in Dark Reign and successfully arranges the (short-lived) death of The Punisher with the help of Wolverine's Anti-Villain son Daken.
Kraven the Hunter's wife Sasha was responsible for the murder of Mattie Franklin (Spider-Woman at the time) and Kaine during the Grim Hunt storyline. (Julia Carpenter, who was going by the name Arachne at the time, was also a target, but was saved by Spider-Man.)
And of course, hundreds of Spidey's equivalents from Alternate Universes were killed by the Inheritors during Spider-Verse. You'd need a separate page to list them all.
Thanos: In The Infinity Gauntlet Thanos literally killed half the population of the universe including many superheroes, and later on in the storyline the surviving heroes would try to stop him, only for him to kill most of them effortlessly (Though this was all undone). At another he literally killed the entire population of the universe including every superhero. In fact, the conflict in Civil War II is caused by him killing War Machine.
Among the deaths caused by Magneto during the tidal wave that the story opens on are Franklin Storm, Angel, Beast, Dazzler, and Daredevil. Following issues also sees Magneto personally kill Professor Xavier and Wolverine.
While it's unclear if she was another causality of the flood or the Blob found and killed her before he ate her, the Wasp still died thanks to a member of the Brotherhood.
Sabretooth kills Angel.
Dormammu kills Dr. Strange Jr.
The Multiple Man killed the majority of the people at the Academy of Tomorrow and Yellowjacket.
Quicksilver murdered Cyclops.
One of Syndicate's heads was blown off by William Stryker Jr. Since they died off-panel and weren't in the main series, it's assumed Stryker's forces also killed Toad and Psylocke.
The Green Goblin killed Spider-Man (though it didn't stick) and Monica Chang.
