This has happened to me now three times, worked last night, I go to work and come home and this is what I get. Only way to fix is delete cfg files and start fresh.
I would really like to know what is going on though:
You’re losing your ‘assets’ directory. It’s in settings > directories. Either set it to where the assets currently live or pick a new spot and then fetch them via the online updater.
Thank you for that.
I wonder how that is happening. It happens randomly…and I am not even messing with settings or any folders. My settings are complete and the only time I add any are when I add new systems/cores and make a new override. Maybe I am inadvertently deleting it or changing my retroarch.cfg directory location for assets, by mistake.
I might oughta do a hard drive test, maybe have some hard drive bad sectors 
At least I know the cause now, I will watch out for it. Thank you.
RetroArch only changes the settings file on exit. Are you user per-core configs or something?