A new character, a rogue scientist - ninja from a long - forgotten clan, could be the main villain. This ninja has been exiled for his unethical experiments. He creates a powerful Frankenstein - like creature and uses it to terrorize villages. His goal could be to prove that his way of mixing different ninja powers through this Frankenstein - like creation is the future of the ninja world. Naruto would be the one to oppose him as he believes in the natural way of developing one's power. He would have to figure out how to defeat this villain and his creation.
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.
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.
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 Orochimaru somehow gets his hands on a Black Lantern ring. He already has a thirst for power and immortality, and with the Black Lantern power, he could become an even more formidable and terrifying villain. He might use it to resurrect his past experiments and create an army of dark minions to take over Konoha.
It could be an unknown, ancient evil that has been awakened. This villain might have powers far beyond what Naruto and Sasuke have faced before. Maybe it's an entity from a forgotten era that was sealed away long ago and now has broken free.
Perhaps an evil Pokemon scientist who has created a device that can control the minds of Pokemon. He discovers Naruto's arrival and sees him as a threat. So, he teams up with some of the most powerful and aggressive Pokemon to stop Naruto. He has no regard for the well - being of Pokemon or the balance of the world, only his own ambition to rule.
A new character could be created as the main villain. Maybe a rogue ANBU agent who was once a friend of Naruto and Sasuke but has been corrupted by power. This character would know all the ins and outs of the ANBU, making it very difficult for Naruto and Sasuke to stop him as he tries to take over the ninja villages using the secrets he learned while in the ANBU.
It could be Orochimaru. He has always had an interest in Konoha and its secrets. Maybe he decides to launch a full - scale invasion this time to get his hands on something he desires.
Perhaps a powerful ninja from another village who has a vendetta against Konoha and the ANBU. They see the ANBU's connection with Naruto as a threat and use their knowledge of the lemon fanfiction element in some way. For example, they might create clones that are disguised as lemon - scented ANBU members to infiltrate Konoha and cause chaos.