After years spent building insanely tough runs and accumulating almost 500 slabs, I am definitely trying out the "one-box" approach. Since I am focused on Golden and Atomic age books and work with a finite amount of cash, it's actually quite easy. I much prefer a few dozen rare, old, and valuable books over a room full of "lesser" issues. It's much easier to breathe now, and my collection consists of books I am truly passionate about. Run collecting requires you to acquire books that you don't really like, simply to fill a hole in the registry or a spreadsheet.
I recently sold two super cool and fairly expensive books to acquire a grail. So I'm liking the idea of acquiring awesome books and selling them to nab even AWESOMER books!
I like the discipline to this approach, because it forces you to be ultra-selective,,.it also frees you up to go grail hunting. I love the idea, and I love the space savings...and as mentioned by another poster, it's much easier to track and maintain your books. I can get my books out of the house in less than a minute if necessary...I can keep a better eye on them...easier to share and enjoy.
A truly massive slab collection can be....anxiety provoking, in my experience.