. . . I recommend ceaning every esp with TESTool, unless the ReadMe states otherwise. (or EE or TESAME if the user knows exactly what to look for) . . .
Why? In my experience, I seem to be better off leaving things alone unless I'm actually getting warnings, conflicts, and/or crashes. I will even run mods with evil GMSTs without incident, although I do clean them as soon as I notice. In the beginning, I wanted everything sparkling clean and I was drawn like a moth to "just fix it" and "Autodelete Unclean". For a long time, I even followed MLOX to a "T". The trouble with these practices is that you don't learn why you're cleaning or moving anything. I learned, through trial and a lot of errors, that sometimes dirty references are activators that *need* to be there, GMSTs are changed for a reason, some mods really *do* need to load after NoM, and not all objects/leveled lists should be merged.
Sometimes, you even find out the reason the author has stated unequivocally that his/her mod *must* load at the end (or the beginning), or must *not* be cleaned/merged, is because they didn't write it in the most efficient, non-conflicting way and not following their explicit instructions will break their mod. In many cases, I've had to either "fix" such mods or just not use them, but this brings me back to my question of Pluto, or anyone else who knows, why clean something if it doesn't appear to be causing any problems?