Random flashing question mark on startup

Every once in a while when my mac mini cold boots, I get the flashing question mark. Turning the mac off, and booting it back up again usually fixes the problem. I ran verify disk permission and verify disk; both came back ok. S.M.A.R.T status was always "verified". I have also booted into single user mode and ran FSCK. No problem there either.
I didn't have this problem until I upgraded to 10.6.3. Just wanted to find out if anyone else is having the same issue and if there is a way to figure out what is causing the problem.

On the face of it, this sounds like a temperature-dependent problem: when the hard drive is cold, it either isn't spinning up on the first try, or the calibration is slightly off and the Mac doesn't recognize the drive as being bootable.
When it is slightly warmer (second try) it spins up, or the calibration is now within limits and therefore it boots and now can pass all the DiskUtility tests.
If it were me, I'd make sure that I had this drive fully backed up onto another external drive -- just in case.
(In terms of it perhaps being a spin-up issue, I'll note that I have 640Gig 2.5" external that doesn't always mount when I turn it on. Generally the second time is a charm. I attribute it to the drive not spinning up.)
Just in case the issue is something else, I'd suggest going to Apple Menu > System Preference > Startup Disk and explicitly setting the drive to be your startup drive.
It might also be interesting to hold down the Option key at startup and explicitly choose the drive. Do this for a few days and see if the problem continues to occur. Holding down the Option key should give the drive a bit more time to spin up.

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