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.
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.
It could be one of the Avengers themselves. Maybe Iron Man, if he feels that T'Challa's technology in Wakanda is a threat to his own tech empire. He might start some sort of power play which makes the Avengers not friendly towards T'Challa.
Voldemort could be a likely main antagonist. He's the most powerful dark wizard in the Harry Potter series. He might see the Avengers as a threat to his plans of total domination, not understanding their world but still seeing their power. So, he could use his dark magic to torture them, trying to break their will before eliminating them.
Perhaps a group of inter - dimensional bounty hunters. They've heard about Loki's children and the potential power they might possess when they grow up. So they target the children to either sell them to the highest bidder or use their powers for their own evil purposes. Tony then has to fight against this group to save the kids.