I have a Mac Mini (2010) that I use as a home server with a DAS (2 drives) attached over USB. Everything is on 24/7.
From all my research online, it seems that spinning hard drives up and down constantly is actually only worse for the drive so I've unchecked "Put hard disks to sleep when possible". Now the internal drive as well as the two externals are spinning 24/7.
The other reason I keep the drives spinning is that if I do have the drives on auto-sleep, I keep getting I/O Errors from the kernel log for my two external drives on USB which was very worrying. Keeping the drives spinning makes those errors go away entirely.
The problem is that the internal drive on the Mini crashed recently and it was only about 7 months old :( Thankfully it was under warranty but the next time I probably won't be so lucky.
This has me doubting my always-spin approach. All the stuff I read previously was for 3.5" server drives, maybe the 2.5" drives are different in this regard and I should sleep them when possible? Or was I simply just unlucky with that crashed drive?
Additionally: Should I want to sleep the 2.5" internal drive, is there a way to sleep the internal but keep the externals spinning? Seems like the pref panel as well as pmset apply the setting to all drives.