I have 11 drives in a 100TB pool, 4 of them are in a USB enclosure, also used for a Plex server. I don't even try to place directories on specific drives anymore. I've surrendered completely to DrivePool and it's been totally stable for years now.
I only allow Duplicated files on the USB drives so the content will usually be pulled from faster ones in the main box, but that's the only micromanagement I do. You can also change your file balancing rules later if you need to move things out for some reason.
I love this software. Fast, reliable, solves a real problem, so much better than Storage Spaces or any of the other sketchy block-based methods I tried.
I've had drive failures and NAS failures, but DrivePool has always recovered gracefully, especially if you get StableBit scanner and let it catch bad drives early.