Well, i followed the post step-by-step by BloodySword http://www.mydefrag.com/forum/index.php?topic=3740.0
and, as explained in step 1 i removed *everything* from the Prefetch folder, files & the ReadyBoot subfolder.
As i intend to run MyDefrag quite often, I also ran it in step 5, perhaps Prefetch will notice *every single folder* that every program touches or looks at, and that's the reason for the HUGE layout.ini file.
After a whole day, I'm quite happy to say that zone 1, where i first place these dirs to the end of the drive, is processed in the blink of an eye, and no files have been moved the last day. I'll keep ProcessMon running in the background to see if i notice some other service/process touch them instead of the one in the screenshot, which apparently only looks at them and is not responsible for moving them around.