A single adventurer could be the main character. This person might be a thrill - seeker who built a shrinking device and decided to explore the human body. Along the way, they make friends with some helpful bacteria and together they face the challenges of the body's inner environment.
Ms. Frizzle is one of the main characters. She's the teacher who takes the kids on these amazing adventures.
Obviously, Bowser himself would be a main character. He is the one whose inside story we are exploring. Luigi could also be a main character if he somehow gets trapped inside Bowser. And some of Bowser's minions like Goomba or Koopa could be main characters as well, as they live inside Bowser's kingdom and might play important roles in the events happening inside Bowser.
Well, Lady could be a young artist named Elizabeth who is always looking for inspiration. And Tramp could be a vagabond musician named Jack. They would meet in the city's art district where Elizabeth is sketching and Jack is playing his guitar on the street corner.
Spyro and a scientist could be the main characters. The scientist is studying the strange phenomena that seem to connect the dragon world and the human world. Spyro stumbles upon the scientist's research site and they end up having to rely on each other. The scientist could learn a lot about Spyro's world through Spyro, and Spyro could learn about human intelligence and technology from the scientist.
The powerful human would be the central character. They might be an older, wiser human who has been sent to Equestria for a specific mission. Then there could be Pinkie Pie, who would befriend the human right away and introduce them to the joys and quirks of Equestria. And there could also be a villain, like Discord, who sees the powerful human as a new plaything or a threat to his chaos - filled world and tries to either befriend or destroy the human.
Obviously, Cortana in her human form would be the main character. But there could also be a scientist who was involved in the process of her becoming human, either intentionally or accidentally. This scientist could be a mentor or a conflict source for Cortana as she adjusts to her new life. Another possible main character could be a human friend that Cortana makes early on in her human existence, someone who helps her understand human culture and values.
A scientist could be a main character. They might use their intelligence to figure out the enemy's weaknesses and develop new weapons or strategies for the human strike back.
Maybe a human scientist who has studied the reapers for a long time could be one of the main characters. He discovers a way to make the alliance possible. And on the reaper side, a young reaper who is more open - minded than the others and is willing to work with humans. The two of them could be the central figures in the fanfiction, with their relationship growing as they face various challenges together.
A young and adventurous driver could also be a main character. They could be someone who loves speed and exploration. In the story, they might accidentally stumble upon a hidden community of sentient cars while on a cross - country road trip. This would lead to all kinds of exciting adventures as they learn to communicate and interact with the cars.
Marinette could be a main character even in this type of fanfiction. If a kwami becomes human, Marinette could be the one to help them adjust to the human world, given her own experiences with the miraculous and the kwamis.