Yes, backup file definitely recommended for large projects! In fact, consider setting up Autosave globally (Inkscape Preferences > Input/Output > Autosave) for all projects.
If you did have to scale or move the entire drawing to a different place on the canvas, I agree that grouping
could be helpful. But since grouping automatically puts everything into one layer, it could also be problematic - especially if there are several or more layers. To me, grouping would not be necessary. I would just 'select all in all layers' and scale and/or move everything at once.
If the reason the entire drawing needs to be moved, is because you changed the page size, and you need to re-center it, there may be a better solution. Have you found Document Properties > Page tab > Page Size > Resize page to content? With that, you would just have to scale the drawing. Then resize page to content changes the page size to match the drawing (or selection). It also offers margins, if you don't want the page exactly the same size as the drawing. So you don't need the extra step to re-center the drawing on the page.
I'm not clear what you mean about layout change. Is this something like an infographic? If you just want to move certain parts or sections, you might be able to use layers to help with selecting the right parts.
(Moini sneaks another message in while I'm typing
)