In what was originally the final storyline of Fans! (they've started making them again) begins as a quest to save the relationship of two recurring TV reporters, which ends when the two of them, as well as Lovable Traitor Desmond Jones attempt to Ascend to a Higher Plane of Existence. They find out too late that they're actually being used to power an Artifact of Doom, which proceeds to wreak havoc, and then the three are never mentioned again. Granted, the main characters have other things to worry about in the short term, but come on, even Kana gets more of a send-off...
Angels 2200 did this to all of Corona Squadron, minus one, with debris from their own ship
In the same battle, Loser suffered the same fate.
Right before the final boss in RPG World, the comic cuts to a sideplot sequence, then back to an unrelated sequence in which the hero is eaten by a random monster. It ends with a closeup of two character gravestones, and the caption "Game Over Forever"
The Last Days of FOXHOUND, a Metal Gear Solid parody webcomic. It takes place immediately before the events of the first MGS game, and the last handful of comics show the lead-up to Shadow Moses. Comic #498 has Liquid Snake grinning like a kid in a candy store, exclaiming "It's happening. it's happening.... it's finally happening" just as Solid Snake is about to get his Tactical Espionage Action on. Comic #499: Dead Decoy Octopus disguised as Anderson, dead Baker, dead Psycho Mantis, dead Sniper Wolf, Vulcan Raven eaten by his ravens, broken Metal Gear on top of dead Grey Fox, dead Liquid Snake. It's not called "The Last Days of Foxhound" for nothing, after all. Of course, Liquid got better...
Liquid: That sucked.
The Other Warriors in Eight Bit Theater were cruelly killed off, likely to resolve their fate(s).
Gaia from Draconia Chronicles. Unlike the two Tigresses who fell in chapter one, who went down fighting, Gaia's death was abrupt, meaningless (she was clearly a noncombatant) and pathetic. Her death doesn't even get any acknowledgement aside from a small passing remark from Queen Oscura.
Every player loses either their real or dream selves in the story, and most of the time it falls under this. Jake's and most of the troll's were even killed offscreen, the former by CD and the latter by Jack.