As others have said, the answer is having different maps.
To add to that: A trick I've been using is when I import a map (Layout), I immediately expand the contents and rename the maps referencing it. This way you can keep track of your various maps and make sure you are referencing (and editing) the correct one.
For Example: I work in Colorado a lot. Sometimes management wants a page sized map for Power Point slides, and other times they want a wall map. I imported both versions from ArcMap and renamed the wall version "<Map>...Size_E" and the Power point Template "<Map>...Size_A". Both maps include an inset map of the entire State of Colorado with an Extent box on them. I renamed one of these "Colorado_Inset_Map" and deleted the second one. I reference that same Inset map on both the wall and the power point sized maps.
I'm sure there are many examples but this is one simple one where I'm trying to leverage this new "Project work-space" environment that ESRI is bringing back with PRO.