I was thinking on a weird concept for a fic last night, not sure if I'll end up writing it though.

While the Simpsons have a picnic, some maniac comes up and shoots Homer and Marge, Bart, Lisa and Maggie quickly make a run for it. Bart and Lisa are then placed on a witness protection program where they have to leave Springfield, but Maggie is not, so she stays with either Flanders or Moe. (I'd be more inclined to go with Moe). Bart tells him not to tell Maggie about The Simpsons.

Maggie is now 11, and thinks that she is a member of the Flanders/Syzlak family. Bart and Lisa's witness protection period is over and the two are allowed to return to Springfield. Bart gives a phone call to Flanders/Moe, to tell him to tell Maggie the truth. Lisa has an exam and cant come initially so Bart returns to Springfield alone. There, he meets with Maggie for the first time in ten years. Various catch up periods occur between him and Maggie, Lisa finishes her exams etc... and Lisa arrives.... etc...

Bart finally decides its time to catch the asshole who killed his parents who is still at large. Tracing clues and old evidence, he figures it out with Lisa and Maggie's help etc...

Then after they caught him, I dunno what happens.

Gazmanafc
Lisa would never abandon her little sister in such tragic time, I'm sure. She'll either take Maggie with them, or stay with her no matter what. Leaving a little girl with such an old pervert like Moe also doesn't look like a good idea to me. Those are two main plotholes, I guess.

Of course, killing away Marge and Homer is angsty, but... fanfiction is fanfiction. Like Kasper said, if executed well, it could work. Just read Jenny's "Yellow Mile" first, to make sure your fic won't have much common with that one.

Gazmanafc
I have no idea how it gets written, if not by you everyone has plenty of their own ideas/concepts...
That relationship you mentioned, was obvious something-made-for-the-plot. Don't get me wrong, I like that episode (it's one of my favorites), but I wouldn't say that that relationship stood after the episode has ended.
Also, I still think Lisa wouldn't abandon her sister. Even if you chain her to the car and ride away, she won't forget about Maggie, right? At first opportunity, she'll run away and come back to her. That's what Lisa would do.

I am more looking in the direction of letting this story take place 5 to 10 years further into the future. This leaving the possibilities of Maggie taking a very active role in the hunt for the killer. This would also make it possible for Lisa and Bart to have jobs that gives them possibilities to do a more effective hunt. Say; Lisa with some education in law school, and working in the justice department. Bart as a police officer or private investigator. And Maggie as the mysteries avenger.

(No. Don’t expect me to write this story.) 

I still don't understand how you will make it convincing to the reader that Lisa had to wait 10 years before going back and meeting Maggie. Just imagine: you live day by day, not knowing about your little (helpless baby!) sister. You know that most probably no-one except you, will care about her and help her to survive. You live with this thought ten years! Such a plot will either make Lisa go crazy, or make her forget about her sis at all. No third option (except coming back sooner, of course). It's not possible to spend ten years and not change...

The story could easily include Lisa trying to run away to search for Maggie. And Bart, doing the same to go find the killer. But if the whereabouts of Maggie were kept secret, they didn’t stand much of a chance.
Now, Lisa is forced to obey  because she is under age. But if the story is set ten years from now, Lisa will turn 18 and thereby being able to do as she wants.
The search for Maggie and the killer is on.