I posted last year about this problem with my mid-2010 iMac. I never had any problems under 10.6.7, but updating to 10.6.8 led to the iMac being unable to fully wake from sleep about one quarter of the time, what I came call being stuck in a "coma" (requiring a hard shutdown and then reboot). As I have the OS on its own partition, I experimented several times by restoring back to 10.6.7, using for a while and noting the results of sleep/wake cycles, then updating to 10.6.8 and again noting. It is clear that simply by updating to 10.6.8 the problem appeared. A representative example from my notes: under 10.6.7, 37 sleeps with 37 successful wakes and no instances of remaining in a "coma" (HD running but screen black and unable to do anything but hard shutdown and reboot); after updating to 10.6.8, 90 sleeps with 70 successful wakes and 20 coma incidents. I should add that during these experiments I made sure not to update any software other than the OS X itself in going from 10.6.7 to 10.6.8, including not installing any software at all while running 10.6.8. It is clear to me that for this computer the issue was coming from 10.6.8. I should add that this was not a wireless issue as I use both wired mouse and keyboard.
Interestingly, we also have a late-2009 iMac, and it has never had any "coma" problems, even under 10.6.8.
Seeing many reports here that upgrading to 10.7 Lion did not make the problem disappear for people, I was reluctant to do that upgrade. I did finally decide, however, to go ahead and upgrade the mid-2010 iMac to 10.7.4, and so far I have not had the "coma" issue after 20 sleep cycles (where under 10.6.8 I would have expected to have 4 to 5 failures to successfully wake). I sure do hope that this is the end of the issue for me because it was not good to be stuck at 10.6.7.