I have taken three recent GA flights, one in the G58 and the other two in the 172 classic, and not getting response from changes with mixture.  Using the Saitek USB quadrant.  I checked the assignment in Controls and that was fine. I could see the mixture lever moving in time with my quadrant movements.  So after scratching my head for a few minutes today I went into Assistance and found that Auto Mixture was selected.  I am 100% certain that I previously had that option set to Off.  100%.  So how did it get back to On?  

I believe I had checked that setting following the previous MSFS 2020 update.  I have flown three or four flights during that span with the DA62, and a flight with the TBM 930.  Both operate with system mixture control.

Is it possible that loading either of these two aircraft somehow resets the MSFS Auto Mixture to On?

I think that must be correct. I have automixture turned off, and I always adjust mixture manually when I fly the Bonanza G36. When I fly the Baron G58, the mixture levers move, but there is no effect at all, except at cutoff. There is a discussion on the Microsoft Flight Simulator forum where someone pulled the EGT simvars from the Baron and found that moving the mixture lever had no effect on EGT or CHT. I'm guessing that automixture is hard-coded for the Baron. This is apparently also true for the Cirrus SR22 GTS in the Premium Deluxe pack.