An interdimensional being that wants to use Loki's unique connection to different realms. This being has the power to manipulate time and space, making it extremely difficult for the Avengers to reach Loki. The Avengers would need to figure out the being's weaknesses and use their own combined powers and skills to overcome it and rescue Loki.
It could be someone who is manipulating Loki to kidnap the Hulk. Maybe an even more powerful villain from the Marvel universe, like Thanos. He might be using Loki as a pawn to get the Hulk for his own evil purposes.
Loki could be a great main antagonist in this context. He's always been one to cause chaos and undermine the Avengers. He could manipulate events to make it seem like the Avengers are causing injustice, perhaps by framing them for crimes they didn't commit. His mischievous nature and magical abilities would make him a formidable foe.
A new character, like a powerful interdimensional sorcerer who wants to merge all the universes into one chaotic realm under his control. He has the ability to manipulate the fabric of the multiverse and can summon different versions of villains from various universes to do his bidding. The Avengers would have to not only fight his minions but also figure out a way to stop him from achieving his goal of multiversal domination.
It could be another powerful deity from either the Norse or the Christian pantheon who doesn't want Gabriel and Loki to team up. Maybe a more rigid and traditional angel who thinks Gabriel is consorting with the wrong crowd by interacting with Loki.
The main characters would surely include Loki, who might be the catalyst for the story. Then there's Thor, his brother, who would try to bring Loki into the Christmas spirit. Hulk could also be a main character in a funny way. Imagine Hulk trying to put up Christmas lights and accidentally destroying half of the building. And of course, the core Avengers like Hawkeye, who could be teaching Loki how to shoot arrows at Christmas - themed targets, and Vision, who might explain the deeper meaning of Christmas to Loki using his knowledge of the Mind Stone.
A new, original villain could also be the main antagonist. This villain could be someone from Percy's past who has a grudge against him and wants to use the Avengers as a way to get revenge. By making Percy betray the Avengers, this villain can not only harm Percy but also cause chaos among the powerful superhero group.
Another possibility is that Death is being controlled or influenced by a greater cosmic entity. In this case, that entity could be the main antagonist. It uses Death as a tool to test or destroy the Avengers. The Avengers would then have to not only deal with Death but also find a way to face this more powerful and mysterious entity behind Death's actions.
It might be an alien race that has the ability to travel through the earth's crust undetected. They are stealing valuable resources from the planet's core. The Avengers, including Quake, are the only ones who can stop them. The aliens' technology and physical abilities make them a formidable foe, and Quake has to use her powers in creative ways to expose and fight them.
A technologically advanced alien race could be the main antagonist. They have studied the Avengers and know their weaknesses. They attack Earth in a way that isolates each Avenger at first. But when the Avengers assemble, they use their combined strength to hack into the alien technology, reverse - engineer it, and turn it against the aliens.
Loki could be a great main antagonist. He might see Nico Di Angelo as a new plaything or a threat to his plans. Since Nico has powers related to the underworld, Loki could try to manipulate him or use his powers for his own evil schemes, which would put him in direct conflict with the Avengers.