It most likely will be Scootaloo's lack of flight ability. It is a great idea for an episode, and definitely would have to include Rainbow Dash in some form. Scootaloo already looks up to Dashie, and they have developed a sisterly bond over Season 3, it would only be logical to continue this into Season 4.
I'd actually like to see Scootaloo not be able to fly, as I think it would open up so many more possibilities storywise, and would also help to further develop her character, as well as RD's.
Derpy is too controversial in my eyes to use. That, and it would just feel weird to see her have her own episode. I mean don't get me wrong, I'd love to see her more in Season 4, but her role as a background character with a couple of little scenes here and there would satisfy my Derpy needs. Oh and add maybe one extended scene where her original voice appears. And muffins, definitely muffins