This is a new one for me. I upgraded a Drupal site from 6.20 to 6.22. After the core upgrade, the block visibility settings are all goofed up. Quite a few that were enabled prior to the upgrade are now disabled. Additionally, the "Page specific visibility settings" are missing for those blocks.
One other clue in this mystery is that, on the main block admin page (/admin/build/block), my three active themes are in a different order. I'm not sure whether that's related, but I've never seen it before.
I do upgrades on a staging server, so my production site is still intact. For now, I'm going to restore the blocks, comparing the prod with staging settings. I'll see if that restores it to fully functional. Regardless, it makes me nervous. I saw no errors or warning during upgrade.
FYI, my general order for doing the upgrade was:
Bam, lots of blocks disabled.
This is a bug. See http://drupal.org/node/1173012