Is it possible to swap/rotate destination backup drives for added safety

Hi @exup and welcome to the forum!

I think you’d generally make new folders in advance, then point Duplicati to the right one for that client.
If for some reason you’re desperate to share a folder, use --prefix to keep backup files distinguishable.

Duplicati works very hard to avoid storing data again if it’s already stored, even slicing files into blocks.
It has a database which is a local cache of certain destination data. Discrepancies will cause problems.

What I usually hear people wanting to do is to mirror the backup elsewhere. You can search the forum.

Because yours sounds like a manual backup after a drive carry, possibly you can have a job per drive.
Once you settle on what gets backed up, you can export the job then import to change the destination.

Guarding against wrong-drive-plugged-in is an issue, but Google found some discussion and answers.

Backing up to multiple USB or external drives?

Windows Drive Letters