For me personally, you'd have to draw a line between a MISB set I already have a copy of or a MISB set that I do not yet own in opened state.
With both it's rather easy. The first one I'd keep as a reassurance, but only if I really loved the set - I'd like the fact that I always 24/7 had a brand new spare copy of it at hand in case of something "happening" to my opened one. I would know I could always take pleasure in a particular set's brand new condition if I ever badly wanted to. And if we're not talking about a set I really like but find rather Meh!: it gets sold in order to buy sets I like!
Now with a MISB set I haven't got an opened copy of, I have to decide what I would appreciate more: said set in brand new condition or the money it would bring if I sold it.
However, I would never ever buy a new set with the strict intention of never opening it. Only if I planned on giving it to someone as a present or passing it on to my children if I ever get any. But that's a different story!
Cheers!
And MISB sets on!