Though Deadpool is a fearsome fighter, he shouldn't be a major threat to a team like the Avengers. Despite this, the Merc with a Mouth has felled Earth's Mightiest Heroes on more than a few occasions, and the most brutal takedown involved Deadpool donning the husk of longtime Avengers villains Ultron.
As its name suggests, 2017's Deadpool Kills the Marvel Universe Again from writer Cullen Bunn and artist Dalibor Talajic is the story of how Deadpool single-handedly kills every single hero and villain of the Marvel universe. Unlike the first time Deadpool did that though, this series has Deadpool being tricked into his rampage. A cabal of every single Marvel Universe villain comes together to brainwash Deadpool so that, while he sees himself goofing off with friends, he's actually slaughtering them. He sees his massacre of the X-Men as a fun science experiment. He sees killing the Punisher and Moon Knight as a harmless attempt at playing basketball with his buds. When the remaining heroes realize that Deadpool's next target is the Avengers, they gather their heaviest hitters to fight him. To counter this, the villains graft Ultron's husk onto Deadpool, making him wear it like an Iron Man suit.
Under the villain's influence, Deadpool imagines the battle as an anime fighting tournament. In his head, he's not murdering the Avengers, he's fighting an onslaught of robot combatants. Though readers don't see him perform the act, the situation's grim reality soon sets in. Completely protected by Ultron's vibranium, nothing could stop him from ripping Iron Man in half, decapitating Dr. Strange, and impaling Black Panther. He snaps Jessica Jones' neck while Cable and Kate Bishop futilely try anything to stop him. Unfortunately, a mistimed explosive arrow from Kate ends Cable before Kate herself is taken out by an energy blast. A part of him rebelling against the villain's programming, claustrophobia overtakes Deadpool. With great pain, Deadpool tears the Ultron suit off and shambles to kill Power Pack and Ms. Marvel.
As alluded to, the main thing that sets Deadpool Kills the Marvel Universe Again apart from its predecessor is how sympathetic Deadpool is. Though Deadpool's first rampage through the Marvel Universe attempts to cast him in a slightly sympathetic light by establishing that he believes he's freeing everyone from the horror of being a fictional character, the suffering shown combined with Deadpool's smug attitude can make it an unpleasant experience for some. In contrast, this casts Deadpool as a tragic hero. Deep down, Deadpool knows he's hurting good people, but that's completely drowned out by his programming from the cabal of supervillains.
Adding to the situation's horror is how the villains give Deadpool a leg up in combat. Instead of elaborate traps or exaggerating Deadpool's fighting skills, he's given tools that make his victory more than believable. Ultron is already one of the Avengers' most powerful villains, adding Deadpool's capabilities and reflexes creates a threat that's nearly unstoppable. Though Deadpool does eventually get revenge on the villain cabal, they already succeeded in making him a force that completely dismantled the Avengers.