A key concept is that sprites and textures are loaded into memory per layout. If you are not running into memory limitation issues, you probably don't need to worry. On the other hand, if you design with changing layouts in mind, your game can be more or less infinitely scalable.
The best way to take advantage of multiple layouts is when loading different tilesets, such as a snowy mountain area versus a desert area. You'll be able to load more detailed graphics per layout within your memory limitations.
Another consideration is CPU utilization such as pathfinding and other off screen processing. Separating by layout can sometimes solve issues with the CPU getting bogged down.