In Phase 5, Kang the Conqueror is the greatest threat the MCU will face, but other villains may give him a run for his money.
When the titular trickster and Sylvie confronted He Who Remains in the Citadel at the End of Time, he was first introduced into the Loki series. This was a Kang variation who warned of a potential multiversal conflict if the Sacred Timeline was not maintained. Sylvie was unmoved and killed He Who Remains, thus, timelines start branching off giving rise to the reappearance of Kangs.
Kang makes his first strike in Ant-Man and the Wasp: Quantumania. He will need Scott Lang's assistance to get back on track, and Kang may negotiate a return for his five years with his daughter.
Kevin Feige, the Marvel President, revealed more about Kang in Empire Magazine, giving us further information about him and his current status in Quantumania. Kang isn't at his full power just yet, and he'll need the help of Scott Lang to get his time and space-traveling ship online. He's also anticipating ruining his family.
Given how important Kang is to the main storyline and how effectively they've been constructing his character, one can never be too certain. There are many big bads that Marvel might exploit to increase the stakes.
The Beyonder was created by a race of ancient beings, and he was once part of an entire universe that existed outside of the Marvel Universe. The Beyonder observes this new world and learns about it. He goes too far, however, when he chooses heroes and villains (including Kang) to battle it out in a battle royal in the Secret Wars (1984) by Jim Shooter, Mike Zeck, and Bob Layton.
The Avengers: A Space Odyssey is expected to be based on Jonathan Hickman and Esad Ribi's comic book limited series Secret Wars (2015). This timeline multiversal battle is at least reminiscent of the Kang's role in the Marvel Universe. However, it might prove to be too complicated to include a living universe among the timeline and multiverse shenanigans.
Galactus is a mathematical system.
Galactus is one of the most powerful beings in the cosmos, and he's older than the cosmos itself. Galan and his crew left the ship and flew into the heart of the largest sun to sacrifice themselves, but while everyone died, Galan remained, and the universe's sentience merged with him as part of the new universe.
Galactus has slaughtered countless animals over the years, becoming stronger by consuming life-energys to feed his hungry hunger. He considers himself the counterbalance between Eternity and Death, and that puts him on a pedestal that might even knock Kang off of his. His consuming of planets is part of our natural order of things.
Galactus was first introduced by Stan Lee and Jack Kirby in Fantastic Four issue #48 (1966), and he has returned many times to trouble the team. They might wait until the Fantastic Four arrive in the MCU, but they might go in a different direction. He has vast abilities of planet-destroying destruction, creation, transmutation of matter, and resurrection abilities.
Dr. Doom is a psychopath.
Victor Von Doom is one of the most evil and intelligent characters in the Marvel Universe. After the deaths of his parents, he continued his studies at a top school, and he accepts, leaving his hometown of Latveria. He goes to America's State University in New York, where he meets Reeds Richards, who later designs his metal suit and adopts the name Dr. Doom.
Dr. Doom's capabilities and abilities are indistinguishable from Kang's, and they're similar in many ways. He's notorious for dreaming big, has no hesitation in crossing the line to accomplish what he desires, and has the will to win a multiverse war. In the original Secret Wars, he's clever enough to steal the Beyonder's powers for a moment, but his insecurities get the better of him.
Supreme Court is strange.
The Ancient One cautions him that saving Christine from the car accident would create a paradox.
The Ancient One splits him in half using the Dark Dimension, yielding a darker Strange Supreme and a good Strange who accepted Strange. Strange Supreme continues growing in power and refuses to give up his quest, and the two Stranges fight. Christine escapes from his deformed, evil form when she discovers him.
Strange Supreme is expected to return to the main MCU at some point in time, as his main objective would be to persuade this version of Christine to fulfill his own desires.
Apocalypse would be a huge surprise and a way to get the character right. Born in ancient Egypt, he was abandoned and adopted by raiders who taught him to keep going. Later, he used Rama Tut's' regeneration technology to become a god to different cultures.
Apocalypse discovered a Celestial spaceship in Mongolia, and he became obsessed with discovering how to unlock this alien technology. Nathan Summers became involved in the battle, and Nathan's techno-organic blood infected his Apocalypse, leveled up his abilities, and allowed him to claim the powerful ship.
Apocalypse has had other live-action versions, similar to the Fantastic Four, so it might be interesting to reimagine these characters in different directions. Although there aren't any known plans yet, with Apocalypse being such an ancient force, he's a big bad who's worthy of a showdown with the MCU's heroes, and a multiverse war might be a viable option.