Is it possible to create a layout to customise the simple edit interface and have it apply to just one site or is it applied system wide?
Layouts are system wide.
You can however use a show_if to change the appearance a design, based on whether the user is logged in or not.
Some people choose to use this functionality to create a "toolbox" to access the different screens of simple edit. In this case, you can obviously apply different designs to different sites.