A 3rd-party utility allows for saving workspaces and settings for individual displays - SwitchResX. I have a rMBP here at the office, attached to two Dell 4k displays - one in portrait for word processing and email, and one in landscape for drafting work. SwitchResX can be set to recall how I want each display, even when one or two is/are turned off. One can also set resolutions for each app, if desired.
Different resolutions, different settings/preferences? No problem. Best $14 I ever spent on my multi-display setup.
We also use it on several iMacs with external attached displays. (I own a small company, and impose my will on my employees. Until they revolt...)
On a related matter - a workspace - I also use Spectacle to "move" or "throw" a window/application from one display to another, using a keyboard shortcut.