2. "What if The Avenger Fought Galactus?" (Volume 2, #41)
In a world where the Fantastic Four died in their fateful rocket crash instead of emerging with superpowers, things end up a bit differently. Namor is left in a state of amnesia (instead of being found and helped by the Human Torch), so he never discovers Captain America frozen in a block of ice. A much bigger difference is that when the dreaded world-eater Galactus shows up hungry, Reed Richards and the gang aren't there to save the day.
The Avengers respond to the situation and things go badly. With very little effort, Galactus subdues each team member without taking a scratch. When Iron Man is teleported to the World Ship to steal the Ultimate Nullifier, he sets off a metal-sensitive alarm (which the Human Torch didn't trigger) and is taken out of commission. With all options exhausted and little hope left, this world's version of Uatu violates his oath of non-interference and steps into the fray to save Earth.
After defeating Uatu, Galactus compromises by devouring his life force instead of Earth... which apparently means that a Watcher is the nutritional equivalent of an entire planet. Feeling a bit remorseful, Galactus takes the body of his fallen foe to the Watcher homeworld so that he can be given a proper funeral pyre. This tale has the distinction of being so bleak as to disturb our narrator who must ponder the mortality of his own alternate self.
1. "What If The Fantastic Four's Second Child had Lived?" (Volume 2, #30)
To be fair, since this issue contains two different stories, only half of it's depressing. But dear god,what a depressing half!
In this universe, Dr. Otto Octavius a.k.a. Dr. Octopus helped Reed Richards to stabilize Sue's second pregnancy. Unfortunately, there are other complications and Sue dies while in labor. This comes as a shock to everyone except young Franklin Richards, who had a dream foretelling this, and is convinced that his sister (named in memory of her departed mother) is a monster.
Over the next few years, multiple people close to the young Suzy Storm die off from the same illness that took her namesake. Alicia, Johnny and Ben, along with every babysitter, teacher and even classmates that come in contact with Suzy all wind up dead. Try as he might, Franklin can't get his father to realize what's going on. When he presses the issue, his dad starts hitting him. So in desperation, Franklin goes to Victor Von Doom for help.
When Doom confronts Reed about the matter, things quickly escalate into a full-on brawl. As Richards is struck down by his arch-enemy, he sees his daughter transform into an H.R. Giger-esque monstrosity and has enough time to apologize to his son before being devoured. Doom sacrifices himself to save Franklin, giving him enough time to blast Suzy through a portal into the negative zone. His victory is hollow and bitter, because now Franklin is all alone.
As I said before, the other half of this issue is a happier story. That makes the first half of this issue the most depressing What If ever written, because even Uatu needed something to cheer himself up afterwards.