Perhaps in this fanfiction, Twilight is poisoned by an unknown enemy. As she slowly succumbs to the poison, she spends her last moments giving advice and passing on her knowledge to her friends. Her death would be a turning point for Equestria. The ponies would have to learn to live without her wisdom and magic, and they might also start to question the safety of their world, which could lead to new storylines about strengthening security and finding new sources of magic.
One possibility could be that Twilight sacrifices herself to save Equestria from a powerful dark magic. Maybe she uses all her magic power to seal away an ancient evil, and in the process, it drains her life force completely. This would lead to a very sad and solemn atmosphere in Equestria, with her friends left to mourn and remember her great deeds.
One possible plot is that Rainbow Dash is caught in a battle between dark magic and the forces of good. She might be overpowered by the dark magic and die as a result. This would be a very dramatic plot as it would involve the struggle between good and evil in the My Little Pony universe.
In some fanfictions, Spike might die heroically while protecting his friends. For example, he could sacrifice himself to save Ponyville from a powerful dark magic attack.
A plot could involve a group of villains from another world who want to capture both Godzilla and Luna to use their powers. They manage to transport Godzilla to Equestria. Luna, being the protector of the night, finds Godzilla and realizes that they need to escape and fight back. Along the way, they meet various other My Little Pony characters who help them in different ways. Eventually, they face the villains and with their combined strength and the help of their new friends, they defeat the villains and Godzilla returns to his own world, but not before a new friendship is formed between him and Luna.
Fluttershy would be heartbroken. She would likely retreat to her cottage for a while, surrounded by her animal friends. But she would also be the one to first start thinking about how to honor Twilight's memory. Maybe she would start a garden in Twilight's name or try to teach the other ponies about the gentle and kind ways that Twilight had. The other characters would look to Fluttershy for comfort as she has a very calming presence, even in her own grief.
In some fanfictions, she could die sacrificing herself for her friends. Twilight is extremely loyal to her friends in Ponyville. So, if there was a situation where her friends' lives were in danger, like from a powerful villain, she might choose to give up her own life to protect them. This would be a very heroic and in - character way for her to die.
The plot could involve Cadence preparing for motherhood. She might have to deal with morning sickness and strange cravings, like eating only the rarest of crystals. Shining Armor would be by her side, constantly worried but also very excited. They could start decorating a nursery in the Crystal Castle with the help of their friends.
Well, the plot could involve Winona entering a beauty contest in Ponyville. She's not used to being in the spotlight like that. When all the ponies start complimenting her appearance, she blushes deeply. She might initially be hesitant but then decides to give it her all in the contest, with her blushing becoming a cute part of her charm throughout the story.
One possible plotline could be that Twilight is influenced by a powerful dark magic artifact. Maybe she discovers an ancient book that slowly corrupts her mind, making her turn against her friends. As she turns evil, she might start to use her powerful magic to take over Ponyville, believing that she can create a 'better' world under her rule.
Well, it could be really interesting. Maybe the ponies would be confused by the ninja world's concepts like chakra and jutsu. They might try to apply their own magic in the context of Naruto's story, leading to some really wacky and creative scenarios.
Well, one possible plot could be that a magical spell gone wrong turns a My Little Pony into a dragon. Then the pony - now a dragon - has to learn to control its new powers. It could face challenges like being feared by other ponies or not being able to fit into its old home. Maybe it goes on a journey to find a way to turn back, meeting new friends along the way who help it accept its new form.