I've had this problem, too. 3 monitors on my main GPU and 1 on the onboard GPU.
I think the culprit is the way Windows enumerates displays, which doesn't always match the GPU driver's enumeration. On top of that, they might have different ways of marking a display disconnected vs asleep (2 of my displays are technically TVs, 1 which doesn't have a sleep mode).
I would recommend saving several different snapshots - after a fresh boot, when the problem appears, once you fix the problem, and once a while after you've used the system a while (plus once after connecting/disconnecting any other displays). Then you can try each snapshot to see if any work. Figure out which works and put shortcuts to those layouts somewhere convenient.
Now, if they could fix the folder portal icons being offset, that would help me stop twitching.