Hi Grizzly.
My MB is the ASRock X570 Taichi which has three slots for M.2 drives. All three are populated (1TB, 250GB, 2TB).
This is what I do: I install Windows on the second drive (250GB) and "decorate" that with all the little third party utilities (music and video processing and other useful stuff), add-ons on the context menu, etc. So this is my clean "prototype". Then, using Acronis true image, I clone that on the first drive (1TB) which is the one I use (drive C).
I may never go back to the "prototype" unless something happens to the drive C installation, usually some adware and occasionally a virus as I do not use antivirus (never did). Rather than wasting time searching for the offender, I install updates (if any) on the "prototype" and using Acronis, make an image and restore it on Drive C. Also, this can be used to run my computer if something happens to actual drive C. That is why I want Windows installed on a different drive but in the same PC.
The prototype I have now is about one year old and highly modified. I need a new one.
All three M.2 drives are plugged in sockets (not soldered) but there is thermal tape between them and the Mother Board cover. Removing the cover, will rip the tape and could damage the M.2 boards. Also, removing a bunch of little screws is a hassle.