Annihilation

This is one of Marvel's most well-received storylines, one that takes place entirely in the cosmic corner of the comics. It finds Annihilus, the bug-like warlord of another dimension, invading the galaxy with a seemingly unstoppable army, forcing characters like Nova, Ronan the Accuser, Peter Quill, and Super-Skrull to form an alliance to even hope to overcome the odds. One part sci-fi, one part war story, the event saw thousands lose their lives, with our heroes as the underdogs, which only makes their eventual victory all the sweeter. Marvel does not own the rights to Annihilus (Fox does), but they could find a substitute of some kind. The important part is that the galaxy is almost brought to the brink of destruction, and is saved by the hard work and sacrifice of a big cast of characters. None of the Earth characters were in the story, but they can always sub in for others. I can see Thanos (who plays a big part in Annihilation) ripping a hole to an invading dimension with the Infinity Gauntlet, forcing the Avengers and the Guardians of the Galaxy to fight completely foreign enemies.

Note: Annihilation: Conquest, the sequel to Annihilation, featured Ultron as the main villain doing almost the same thing that Annihilus did. It'd be pretty logical to mix the two and have Ultron return in the wake of Infinity War with the whole universe in his sights.

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