There could be a group of powerful out - of - world beings who are interested in the chakra of the Hokages. They revive the Hokages themselves, but with the intention of stealing their chakra. They are extremely powerful and have abilities that the ninja world has never seen before. Their arrival shakes the very foundation of the ninja world and forces the Hokages and Naruto to come up with new strategies to defeat them.
Well, it could start with Naruto accidentally stumbling upon an ancient artifact that has the power to revive the Hokages. Once revived, they find that the ninja world is facing a new danger that is slowly corrupting the chakra of all ninjas. The Hokages then decide to train Naruto and the new generation of ninjas in a special way to combat this threat. They share their unique experiences and skills, and together they form a plan to save the ninja world from this new catastrophe.
It could be a new and powerful enemy that the past Hokages once sealed away. With Naruto's revival of the Hokages, this enemy somehow gets released or starts to break free from its prison. This antagonist would be extremely powerful, having been a threat that required the combined efforts of the Hokages to deal with in the past.
Perhaps an ancient evil that was sealed away long ago is awakened when Minato is revived. This entity could be a powerful demon or a dark ninja from the past. It wants to destroy the ninja world and Minato stands in its way. Minato, with his skills and knowledge, has to figure out how to defeat this ancient evil with the help of Naruto and the other Leaf Village ninjas.
Obviously, Naruto himself is a main character as the story revolves around his revival. His friends like Sasuke, Sakura, and Kakashi are also likely to be main characters. They would be involved in the process of bringing Naruto back or in helping him adjust to his new life after revival.
It could be Orochimaru. He's always interested in new forms of power and experimentation. He might see Wolverine as an interesting specimen to study and try to extract his healing factor or adamantium for his own purposes. This would put him in direct conflict with both Wolverine and Naruto, who would naturally oppose Orochimaru's evil plans.
Danzo could be a great main villain in a Naruto Frankenstein fanfiction. He's always been power - hungry and secretive. He might use the concept of creating a Frankenstein - like being to gain more power for Konoha in his own twisted way, but really it's all about his own control. He could be using parts of dead ninja's abilities or something like that, and Naruto would have to stop him.
Orochimaru could be a likely main villain. He has always been interested in Naruto's power and body. Maybe he finally devises a plan to kidnap Naruto and use his body for his own reincarnation experiments.
It could be Orochimaru. He might be interested in stealing the exosuit to enhance his own powers and immortality research. He could see the exosuit as a new way to achieve physical enhancements beyond what his current jutsu can do.
Another possibility is that the main villain could be a spirit or entity that has been trapped for centuries. It uses its influence to make the Hidden Leaf Village conduct 'experiment 101' on Naruto. The spirit hopes to use Naruto's body as a vessel to be reborn into the world and wreak havoc. So it manipulates the events and people involved in the experiment from the shadows.
Maybe an old enemy who was thought to be defeated but has somehow returned stronger. Orochimaru could be a possibility. He was always obsessed with power and immortality. If Naruto is revived, Orochimaru might see it as an opportunity to study Naruto's new state of being (since he was revived) and use that knowledge for his own dark purposes.