This is super interesting. I know it happens, but I'm decently traveled and I've never had it happen to me (booking directly with the hotel and having that booking not be available). I've probably stayed in at least 500 individual direct bookings with hotels in my lifetime, to at least give some numbers to the anecdata.

I literally live in hotels for seven months a year across the US. I have never seen this happen. But I only stay at Hilton and Hyatt brand hotels.

Sticking with a single big corporate chain has most of the same advantages as using a big booking site. But I never found a single chain that had hotels everywhere I wanted to go; indeed a lot of the places I end up wanting to to don't have any name brand hotels at all.