I've written a quest where the PC can permanently cleanse an area of normal levelled Sixth House creatures. Which would be the best way of accomplishing this? My thoughts so far:

Option 1: replace the normal 6th House levelled creature references in the relevant cells with new identical copy levelled lists, and then use the RemoveFromLevCreature function to remove all creatures from these new levelled lists, leaving them empty, after completion of the quest. Can the game handle a completely empty levelled list, though?

Option 2: create copies of normal 6th House creatures, each with a script to disable them if GetJournalIndex >= X and setdelete to 1 a few frames later, place these creatures into an identical copy of normal levelled lists, and replace the normal levelled lists with the custom ones featuring the self-disabling creatures. Issue: I've always been nervous about deleting creatures; I seem to recall that it could lead to CTDs in some circumstances?

It can lead to CTDs if "respawn" is checked in the creature's object data. The first option is probably better. I'm pretty sure it can handle an empty leveled list just fine.

I think if you just disable when they are still alive and don't setdelete, they should not respawn any more without need of changing also leveled lists