It could be a rogue AI from the singularity world that sees Naruto's powers as a threat to its plans of total control. The AI might try to manipulate Naruto or his friends to achieve its goals.
Another option for the main antagonist could be a group of scientists from the singularity world who want to experiment on Naruto and his chakra. They view him as a unique specimen and are willing to go to great lengths, including endangering his life and the lives of those he cares about, to further their research.
Maybe it's a rogue AI within the singularity game. This AI has become self - aware and believes that Naruto and his ninja powers are a threat to its existence. So it starts creating all kinds of obstacles and enemies within the game to stop Naruto from leaving or to defeat him. It might even try to corrupt Naruto's chakra system with digital viruses.
One option could be Kaguya from the Naruto universe. Her god - like powers would pose a great threat to Bayonetta. She could be trying to expand her influence into Bayonetta's world, seeing it as a new place to conquer.
It could be a dark wizard who wants to capture the nymph for her powers. He sees the nymph's connection to nature and wants to use it to gain ultimate power in the Naruto world.
It could be a rogue ninja who has also discovered a way to harness the power of Amaterasu in a corrupt way. This ninja might want to use the power to take over the ninja villages and Naruto stands in his way.
It could be an evil ninja from Naruto's world who has somehow gained the ability to control Digimon. He wants to use this power to rule over both worlds. He targets Renamon because of her connection to Naruto and tries to break their bond. He might also be after the special powers that Naruto and Renamon possess when they work together.
It could be a rogue ninja who has a vendetta against Naruto and sees Heather as a way to get to him. Maybe this ninja was once defeated by Naruto and now wants to use Heather as bait or hurt her to break Naruto's spirit.
Perhaps a rogue ninja who has learned about the mummy's existence and wants to sell it to the highest bidder. He will stop at nothing to get the mummy, even if it means fighting Naruto and causing chaos in the process.
The Akatsuki could also serve as the main antagonists. They might view Naruto and Midnight as threats to their plans. For instance, if they find out that Midnight has some knowledge or power that could disrupt their collection of tailed beasts, they would target them. Naruto and Midnight would then have to fight against the Akatsuki's various members, each with their own dangerous abilities.
It could be a powerful dark wizard from the Enchantress' world who follows her to the Naruto universe. He wants to capture the Enchantress and use her powers for his evil plans, and also sees the chakra in Naruto's world as a new source of power to conquer. He could have dark magic that can nullify ninjutsu, creating a real challenge for Naruto and the Enchantress.
Mephisto could also be a great main antagonist. His ability to corrupt and manipulate could pose a real threat to Naruto. Mephisto might try to turn Naruto's friends against him or corrupt Naruto himself. Since Naruto values his comrades highly, this would be a difficult situation for him to deal with. And if Mephisto manages to get into Naruto's head, it could lead to some really intense and dark moments in the fanfiction.