I have a 27" iMac with an Apple Cinema HD display connected. Under Yosemite, I had "Displays have separate Spaces" unchecked in System Preferences>Mission Control to allow an app which requires a lot of screen space to spread its windows out, but still have them appear together when I switched to that Space. Enabling "Displays have separate Spaces" breaks this necessary association for the second display, so I turned it off.
Today I upgraded to El Capitan and was instantly floundering the moment I tried to move from one Space to the next. After the three-finger-swipe the screen appeared to move by the horizontal size of the lower-resolution Cinema HD display times two, rather than the sum of the two displays' horizontal resolutions. This left the menu bar visibly offset from it's normal position. After a couple of swipes, the system was virtually unusable.
When I was able to get to the Finder's Recent Items menu, choosing a particular app correctly displayed that app's Space, but the pop-up Dock was not always completely visible or didn't respond to clicks. Re-enabling "Displays have separate Spaces" at least allows me to use the imac again.
I am not prepared to downgrade back to Yosemite, so I'll be suffering until this gets fixed. I remember something similar happening with a previous OS X upgrade (maybe Lion), though that was probably only a change to the default setting of that Spaces preference.
