My two cents is make sure you leave room to remove any appliances when you build it check their size and how much space needed to move them, they have shorter life spans than layouts. I remember reading on a double decker layout years ago, not sure it would work with O gauge, but is a great space multiplier. use a lower level for a major yard, and require helper engines to get back out, a machine shop area. Something that looks good even with a short ceiling, low sky, under a solid straight away that is easy to reach and see above comes to mind.
Most important have fun and share the good times and good luck.
