In the Blekko cluster we have just under 10,000 drives. We have a two 20 drive 'boxes' (40 drives) from Western Digital, as drives fail we pull replacements from the 'new/refurbished' box, and we put the dead one in the outgoing box. When we get up to 20 we RMA them in bulk, 20 go out, 20 more come in. That becomes the new 'new/refurbished' box.
It really isn't SAN vs non-SAN it is all statistics.
That said, if you're running your ReadyNAS with raid 10 (mirrored drives in a RAID 0 config) you may find some unpleasantness when a drive does fail. Statistically you have a 1/10 chance of not being able to re-silver the mirror for a 5900 RPM desktop SATA drive. That gets a bit painful.