11. Iron Man
While 2006's Civil War arc saw a whole multitude of casualties across the heroes and villains of Marvel Comics, one of the first people to lose their life during this battle was Happy Hogan. And in Iron Man Vol. 4 #14, it's implied that Tony Stark was ultimately responsible for ending the life of his long-time friend.
The majority of Civil War's deaths involved grand spectacle and brutal action, yet Happy's was a far more sombre affair.
In an attempt to lure Stark out into his crosshairs, the Spymaster ambushes a dinner date of Happy Hogan and Pepper Potts, with the rogue threatening to kill both of Tony's close pals. Not taking too kindly to this, Happy lashes out at Spymaster - which unfortunately results in the pair falling several stories to an unhappy landing.
Following this fall, Hogan is left in a coma. In one of the more poignant parts of the larger Civil War arc, we see Tony and Pepper struggle with the reality that is now in front of them.
Appealing to Tony to use his Extremis-based abilities to put Happy out of his misery, Pepper regales Stark with a story about a boxer named Cobra McCoyle. After a career of being hit in the head, McCoyle was unable to look after himself or even feed himself - something which Pepper says Happy specifically said he never wanted to be like.
Shortly after, Happy Hogan passes away, with it implied that Stark used his tech to end his dear friend's suffering and shutdown Happy's life support.