Maybe it's an ancient evil that was sealed away long ago and the colossus contract is the key to its release. This evil force would be the main antagonist as it tries to break free and cause chaos in the ninja world. It could be something like a powerful demon that was once defeated by the first Hokage but is now on the verge of coming back because of the colossus contract. Naruto would have to stop it with the power of the colossus.
Well, it could be about Naruto making a unique contract with a colossus. Maybe the colossus has some special powers that Naruto needs to defeat his enemies. He might have to go through some tough trials to seal the contract.
It could be someone who is jealous of Naruto getting the monkey contract. Maybe a rogue ninja who wants the power for himself.
The main antagonist could be an ancient snake spirit that was bound to the contract. This spirit might not like the idea of Naruto, a human, having control over the powers of the contract. So it tries to possess Naruto or drive him insane by constantly whispering dark thoughts and trying to make him use the snake powers for evil. It would be a battle of wills between Naruto and this malevolent spirit.
It could be someone from the Naruto universe who doesn't like Naruto's newfound fascination with Aku. For example, Danzo might see Naruto's interest in Aku as a threat to the stability of the village and try to stop Naruto from further exploring Aku - related things. So, Danzo could be the main antagonist in this case.
It could be a bully in the village. This bully could constantly pick on Naruto because of his status as the Jinchuriki of the Nine - Tails. He might try to steal Naruto's food or prevent him from playing with other kids.
Madara Uchiha could be a great antagonist. His powerful Sharingan abilities and his grand plans for the Naruto world would put him at odds with Supergirl. He might see her as a threat to his control and try to manipulate or defeat her. Another option could be Kaguya Otsutsuki. Her god - like powers and desire to reshape the world would clash with Supergirl's values and her attempts to protect the people of the Naruto universe.
Kabuto could also serve as the main antagonist. He is a sly character. He might enter the race with the intention of gathering data on all the participants, especially Naruto and his friends. He could use his medical ninjutsu to enhance his own racing abilities in unfair ways, like numbing pain to push himself further or using some sort of drug - like jutsu to boost his speed.
A powerful rogue ninja who wants to steal the Nanosuit from Naruto could be the main antagonist. This ninja might have his own reasons, like using the suit to take over the ninja world.
It could be one of the powerful Deadman characters who see Naruto as an intruder and a threat to their world.
It could be a new villain who has emerged during Naruto's absence. This person might be after the power that Naruto holds or wants to destroy the Hidden Leaf Village for some unknown reason.