Saving them should be an option. I don't ever change my UI settings.
Most of the .persist files I have are from helping people test out their stuff in Help/Tech or chat. They pile up quickly, and I don't need them because I'm only looking at their .cap for a couple of minutes and then forgetting about it.
And if I need to just pop open a .cap to check something really quick and I'm closing it right away then hey, another .persist file that I have to drag to the trash.
Anyway if I did need a .persist file then I would like to say "save a .persist file" so that next time I open stuff I will know where I left off, but most of the time I don't care and I actually prefer to open my files on the first layout without having five different tabs open.
They're a nice idea, don't get me wrong... but they would be so much nicer if I could turn them off.