Here's my setup: MacBook Pro 15", late 2013, running 10.11.6 El Capitan, although this problem has persisted ever since buying my two 2big 12TB drives in late 2013. And during that entire time, I've had other disks attached and have never had a problem with any of the other disks. Those other disks include several LaCie Rugged drives, both Thunderbolt and pre-Thunderbolt, an HD MyBook, and a G-RAID. Two of the Ruggeds are 4TB Rugged RAIDs.
I've narrowed it down to this: when I wake the MBP from sleep, it takes over a minute for the 2big to spin up and mount. By that time, I've already signed in and get the error message. But if I take a really long time to enter my password, so that the 2big mounts before I hit return, the 2big performs normally... at least about 75% of the time. The other 25% of the time, it fails to mount for reasons I can't explain. And if it ever fails to mount, there's nothing I've found to bring it back short of restarting the MBP. Disk Utility can't even see it.