In my small corner of technology (AV) I regularly use three products with physical USB license keys: Crestron VC-4, Scala Digital Signage, and Dataton Watchout. Two of them have a "virtual license key" option that costs extra, intended for use with a VM. I wish they were more rare...

I once had a goon glue the mouse and keyboard ports and fill the unused USBs with glue.