To me, the most likely time for failure would be during a state-change (on-off-on, etc). Because of modern low-friction bearings and lubricants, once you get the disk spinning up to speed, it takes very little energy to keep it spinning. However, after you turn the disk off and let it spin down, it requires quite a bit of energy to rapidly bring it back up to operating velocity, and puts the disk under strain of acceleration. This strain can shorten the disk's life expectancy, costs power, and gives you a performance hit as the disk must be spun up before access.
Media Computer Specs
ASUS H87M-E LGA 1150....Intel Core i7-4770 Haswell....Intel Network Adapter....8GB DDR3 SDRAM....Windows 7 x64.....Plex....Drobo 5N....Drobo Gen2