https://www.scirra.com/manual/183/memory-usage
Images are loaded into memory per layout. In games with large levels and/or lots of artwork, video memory is often the limiting factor.
As far as rendering/processing speed, you can also separate your event sheets per layout, so you don't run through a bunch of events that don't apply to the current layout, but I believe the performance effect is negligible/irrelevant.
Edit: The biggest factor is the initial download time/size of your game - if you have tons of layouts and assets, those will all need to be downloaded when you first load your game.