To answer a few questions:
"Validating files" every time should be fixed by this change.
We'll migrate certain user config files to the new directory when the real game is converted. (But probably not custom content. That will just stay in the old folder and you can move it to the appropriate place.) We didn't do that for the TF beta, though. We'll have a blog post that explains more details about that when the time comes.
Dedicated servers use the same VPK's as the client.
This update will not add the L4D ability to dynamically add/remove addons. You will have to restart the game. But it lays the groundwork to add that at a later date, as well as Steam workshop integration. This is definitely something we have in mind.
VPKs volumes are split into 100MB-200MB chunks. So FAT32, etc is not an issue. (They still can be accessed as a single logical volume by the VPK tool and GCFScape, sort of like multi-part .RAR and .ZIP files.)
Users of the TF beta are reporting their boot and load times have been cut in half.
We expect to retain all existing functionality for all different ways to customize the game. All existing custom maps should work without modification.
There should be no reason to edit or rebuild the game VPK's. You can override any existing file and drop it loose into a subfolder in the addons directory, and it will take priority over the game VPK's.
More questions? Keep 'em coming.