Shamelessly inspired by I Am Legend.
It's been about ten years since Princess Celestia disappeared. Ten years since her disappearance changed Equestria forever. Ten years since nearly everyone became vampires.
But Twilight's not keeping anniversaries. Heck, she can barely remember her own birthday now. But that doesn't matter. She's had more important things to do, such as defending herself from the mindless vampires that attack her every night, and hunting them during the day, where she, as the only one not a vampire, has an advantage. She's killed ponies so often that she regards all the blood as a mild inconvenience. It's just the daily grind.
Or at least, it was until she left Canterlot. Her life there had become unsustainable, and so she took the train that ran through Canterlot to a small town far away on the edge of the Everfree forest- Ponyville.
There, things were different, as she discovered when she collapsed near the edge of the forest. A vampire took care of her, and that was just the start. A sequence of events leads to her making a momentous discovery:
Not all vampires are mindless. The denizens of Ponyville drink blood and sleep during the day, sure, but they're polite, friendly folk who befriend the refugee Twilight. She begins to integrate into the community, and her life seems to be looking up.
Of course, her blood-spattered past will not let her go that easily, and worse than vampires hide in the darkness. Twilight will have one last fight to keep her past from dragging her down and the future from overwhelming her. But she will fight. She has fought since she was a filly. She can win. She can hope.
After all, she is legend.