I do most of my layouts starting with a 12x12 square at 300 dpi. After the layout is complete, then I rescale to the actual size I need for upload or printing. It's super easy to shrink a file, but you can lose quality if you try to scale it up to much.
Rather than size, I think shape. My layout will either be a square, a rectangle, or a circle.
I encountered this exact situation yesterday- I was working on an altered foam die project for a convention (Origins) next week. I made all of the layouts 12x12, and then resized them to 3.5" x 3.5" for printing. It was SO easy!!!!! However, I still have the original 12x12, on the off chance that I might want to print them off for the kids' books, or another project.