Well, perhaps the story could start with Mega Man being exposed to some strange energy or a malfunction in his system that causes the transformation. Then he might have to deal with the new physical form while still facing his usual foes. Maybe he'd discover new abilities or weaknesses that come with being a girl.
Well, it could still be Dr. Wily. He might see Mega Man's transformation as an opportunity to finally defeat him. Since Mega Man is in a new and potentially vulnerable state, Dr. Wily could try to take advantage of that. He might even have some new schemes that are designed to specifically target a female - bodied Mega Man.
One possible plot twist could be that as Spider - Man turns into a girl, he (now she) has to deal with different social expectations. For example, the male - dominated superhero world might react differently to a female version of Spider - Man. Maybe she would face more scrutiny or different types of challenges from the media or other superheroes. Another aspect could be her relationships. Peter Parker's friends and family might have a hard time adjusting to the change, and his romantic interests could take a whole new turn. For instance, his previous female friends might see him in a new light, or he might attract different kinds of admirers as a girl. Also, the way she uses her powers could change. Maybe she would be more graceful or use her femininity in combat in a way that's different from the traditional male Spider - Man.
Well, one possibility is that Mega Man discovers a time - warp device malfunction and gets sent to a future world full of advanced, but also menacing, robots. He has to figure out how to adapt his old - school combat skills to deal with these new - age threats.
A possible plot could focus on how Tails' daily life changes. As a girl, she might have to deal with different social expectations. Her hobbies and interests could shift slightly. For example, she might be more interested in certain types of fashion or more nurturing activities. Her relationship with Amy could also change, perhaps they become closer friends as they share more 'girly' things. And Tails' mechanical skills might be seen in a new light, as she uses them in a different way to solve problems in her new form.
Well, one possible plot could be that Sans somehow gets hit by a strange magic spell. As a girl, he/she might struggle to fit into the existing relationships in the Underground. For example, Papyrus might be really confused at first but then tries to be supportive. And Sans (as a girl) could also have different interactions with Frisk, like maybe a more motherly or sisterly bond.
Well, perhaps in the fanfiction, Ash is exposed to a mysterious Pokémon's special ability that causes the transformation. As a girl, Ash discovers new aspects of himself. He might find that some Pokémon are more attracted to his new form and are more willing to be caught or trained. He could also use this new identity to his advantage in battles, like using the element of surprise against opponents who are used to facing the male Ash.
In a fanfiction where Nagisa turns into a girl, it could be part of a wish - fulfillment scenario. Nagisa secretly wished to experience life as a girl for a day, and some supernatural being grants that wish. As a girl, Nagisa has to navigate through daily life, school, and social situations. There could be humorous moments when Nagisa tries to act like a girl but still has some of the old habits from being a boy, like being too rough during sports in a girl's body.
Well, in a Todoroki turns into a girl fanfiction, perhaps there's a villain who has a transformation quirk and uses it on Todoroki as a form of psychological warfare. Todoroki, now a girl, has to find a way to reverse the effect. In the process, he/she realizes that society treats female heroes differently and has to fight against those prejudices too. Maybe he/she even uses this new form to her advantage in some battles, by using the element of surprise.
One possible plot could be that Cloud, after turning into a girl, has to adapt to a world that now views her differently. Maybe she struggles with newfound emotions and social expectations. For example, she might have been a tough warrior as a male, but as a girl, people underestimate her. She then has to prove herself all over again in battles or quests, while also dealing with her own internal confusion about her new identity.
Well, perhaps the story could start with Keith being exposed to a strange energy. This energy alters his DNA, turning him into a girl. As a girl, he finds that he's now treated differently in society. He uses this experience to understand the struggles that girls face. He might also have to adapt to physical changes like different body strength and new ways of expressing emotions.