Layouts are like scenes or levels in other game design programs.
You can use one layout to design your whole game if you like (my Capt. Doe Saves the Universe is one gameplay wise... I use two more though one for options/help menu and other for splash screen... I think in Clicker Wizard I used just one layout and used a layer for splash screen...).
If you made a game like angry birds for example, each "level" would most likely be a new layout you designed. Same with a platformer like Mario.
If you made an infinite runner/jumper like flappy bird you would only need one layout and spawn objects on it.
Each layout can have layers, so each one is a new canvas to create on. Objects you spawn into the world via events only have to exists at runtime somewhere on a layout so some people make a specific layout they use as a sprite storage only... You can use the global layout toggle to make the status of items on one layout be remembered on future layouts as well.
Each layout can have its own event sheet if you want too.