Okay, so I tested some things out. I checked out the prefs.json file and did some VaM start ups to see if it and when it changes (opened in notepad++ with hot reload). Read/write rights was not the issue, the file could be wrote to. I also see settings changing in the file instantly when I change the preferences in VaM. When I shut down VaM (either shutdown button or hard close or alt+f4), the new settings remain saved in the prefs.json, so that's good.
However, when I startup VaM again, it immediately changes the settings back to the old ones. I did a hard reset and default settings reset of VaM, still the same issue. Cleared and disabled caching, still the same. Temporarely removed all my addons and saves to do a clean startup. Still the same issue. It's quite strange, since when I change the settings in VaM, I would reckon the old settings are simply 'gone'. I'm not sure why it defaults back to the old ones. Especially because the aren't 'normal default settings'. E.g. render res was at 0.9.
Anyway, I kind of gave up and just did a full clean install of VaM. This kind of forced me to cleanup all my saves and addons anyway (been postponing that xD), so thats good I guess. Well, it solved the problem. Everything workes properly now. Still boggles my mind though.
Nevertheless thanks for the help. And yes indeed, for future readers, don't start VaM with admin rights if you're running custom scripts!