Layout size doesn't matter. The amount of memory used does.
You can't just shovel a bunch of assets in, and hope for the best. You can swap textures, but you have to be careful of when and how its done.
So basically, what you described on one editor layout? Probably not.
Programatically during runtime? Sure. In fact this is one descriptor away from an endless layout.
You will need to know which objects with instances share the same texture, and which don't.
Then you will have to figure out how to balance the swapping of textures, and the timing.
No game will have a background with elements that are never repeated.
All games repeat certain textures with variations in size, and orientation.