More than 50 frames?

[Ai]

pkjo: ah, that's a *workflow* question.
(incidentally, it's completely orthogonal to the question of whether you work with 1 layer/frame or 1 image / frame.)
What you describe is a very common process among animators, because that is a pretty effective method.
I used it to make this yesterday:

however, it has larger stages. As a rule, first the key frames are done, then the same process is used to fill in in-between frames, and once the whole animation is looking good, it's rendered (previously being just outline, thumbnails, silhouette or flat colors)

If you're talking about multiple independently-animating objects, these are usually individually animated then inserted into the animation as an animation (on their own layer or similar.). I definitely recommend something advanced like GIMP-GAP  for such an application. Layers and comfortable support for 'sub-animations' are a must for such projects.

[pkjo]

What you describe is a very common process among animators, because that is a pretty effective method.
I used it to make this yesterday:

Just to clarify, you're referring to the editing images and not the layering method right?

Key frames? I thought that was something usually done with the layering technique. I guess it's something all animators do. Personally I've never tried but it seems like an efficient method. I'll be sure to give key frames a go 

[Ai]

Just to clarify, you're referring to the editing images and not the layering method right?

Yes, I did that with GIMP-GAP, which uses 1 image per frame.
I used to use the layers method, but I found it too limited (and somewhat awkward)

Key frames? I thought that was something usually done with the layering technique.

You may be thinking of onion-skinning (which is certainly a vital tool when drawing keyframes).