For "normal prose", I suppose automatic layout would be feasible. However, for complicated (scientific) documents, I'm not very hopeful that this can happen without human intervention.
For my
book (shameless plug) I made a
specially formatted version for 8" ebook readers (I have an iRex iLiad myself) and that was a
lot more work than just changing some parameters of the geometry package. I had to move illustrations around, and even re-word some of the paragraphs to fit. Fortunately, I did manage to include both versions in the same source file, so I can select at "compile time" which format I want. But doing this again for a 6" version or perhaps a separate 10" version would be getting progressively more difficult, and I'm not sure the extra sales would warrant the effort.
I do think that extending PDF as a "container" which has multiple pre-rendered versions is a pretty good idea, and much more elegant than having to keep different files around.