How did you go? Any luck?

NTFS does not have the permissions structures Linux native filesystems have. All sorts of problems come from using NTFS for executable files. That said, exfat seems better in a bunch of ways, maybe try that?

What is a CHA score? I can’t find something that fits the initialism with any relevance, certainly not a CHADS score (stroke risk).

What do you do with a faulty RAID drive? Early in the morning!

Oh, great, that actually limits what it is a lot. If it were related to video we could spend ages looking at codecs, drivers, all sorts of stuff.

If it happens in all windows including winecfg we have to be looking at a few causes.

Do you have a high polling rate mouse? That can cause a stutter issue. To test remove the mouse before launching something in wine (by terminal if you have to), then see if it replicates the issue. If no change, move on, next item.

You could be having a problem with your audio system trying to give things too quickly and falling over itself. Prefix the wine command with the below line.

PULSE_LATENCY_MSEC=60

So it would be something like

PULSE_LATENCY_MSEC=60 winecfg

That should stop it if it is that audio issue, so see how you go.

Lastly, if you have winecfg running it is slowing itself down, but is it impacting other programs as well? I assume so, but want to make sure, so if you are for example playing a video in your browser and then launch winecfg does it start stuttering the video?

If none of the above helps can you dump the output of ps , mount, lspci -k, and iostat while no wine is running and while wine is running? Iostat is in iotools in mint I think, you may need to install it. Also, probably use a pastebin for the outputs.

You may be having a disk seek issue. Are you on a spinning disk? If so, sometimes running something a couple of times will have some cached or at least have the heads in the right spot to read the needed data. If that is the issue upgrading to an SSD would probably solve the issue at the root. A possible test would be using a RAM disk if you can be bothered testing it, you have sufficient RAM that it may be viable depending on the game.

That all said, for next steps I would personally consider if maybe an older version of WINE would work. Could you try installing another older version of both the vanilla and GE versions? Also, did you update your nVidia drivers recently? Maybe roll back if your system will work with that, I can do it easily in EndeavourOS but Mint is not something I am recently acquainted with, it may be a real pain or may tank your driver install to try and roll back. Also testing installing a browser in WINE and loading a video that way may help troubleshoot, or VLC through WINE and native to compare. Ultimately you want to try and find the difference between the failed states and the working states, so if you come back bring a log from a working run and a failed run.