I routinely work with mobile and desktop setups. I usually keep a copy of media on a portable drive and SAN synced with chronosync. Keeping everything on one drive has a bit of an advantage in that it’s easoer to manage, but performance may not always be optimal.
As far as safety, having a portable and desktop setup is more safe as everything is in two places at least.
Chronosync, or similar, helps keep all the media and versions in sync between disparate drives.