For me, it would depend on how complex the image in the middle is. If it's something a circle or star, then I would not use layers at all, because that would be a very simple file.

But if the middle image is something like photorealistic vector drawing, I would certainly use layers, because that will be a very complex file, which might well present performance issues, and then layers could help with the performance issues.

I'm assuming by your wording that the middle image would be an imported raster image. If that's the case, I would not bother with layers at all. Well, not unless your ultimate goal for this image is to send to a screenprinter, to put on fabric. As far as I understand, layers are required for that -- one layer for each unique color.

Info on layers, in the manual: http://tavmjong.free.fr/INKSCAPE/MANUAL ... ayers.html

Once I create the layers/sub-layers, I should be able to add objects to each layer/sub-layer. Right?

It doesn't matter whether you make the layers first, and draw the image second; or draw the image first, and make the layers 2nd. Whatever works best for you.