Depends on its use. Time Machine and other backup services are expecting a drive to be mounted. Certain workflows and external instances of things like Photos libraries, iTunes libraries, Lightroom libraries, etc. are all looking for a drive that is mounted consistently, lest things get all screwed up. File storage and archive drives can certainly be unmounted, but then you need to remember to disconnect them in order to reconnect them. It can get to be a pain.
Consistent, reliable drive connection depends on the workflow. You know yours, so you know the answer.
