I thought I was losing it until I found this thread. I use Macs 10 hrs a day, since they were created, various models, at work and at home, and I've never seen this. Just today, I had the same experience: about 2/3 of my apps disappeared: DevonThink, MSOffice apps, iWork apps, GuitarPro, Garageband, iPhoto, iTunes, a number of my own custom apps, Acrobat, Parallels, Chrome, Firefox, etc... But not all. Completely random. As if someone walked up to my Mac, selected a number of them, dragged to Trash and emptied. Terminal also showed they're gone, so not a Finder glitch. Question marks over the corresponding Dock icons, just like the rest of you. Curiously, GuitarPro was actually left running on another account, while its app disappeared from the Applications folder!
Repair disk found a few minor problems like always. No luck in recovering the apps tho. However, after restart, iTunes magically reappeared, but no others.
I spent the better part of my afternoon reinstalling the missing apps which seem to work fine now.
And now for the most unbelievable part: just this evening, after I restored my apps, my wife, also a long time experienced Mac user, just called down to say her Parallels app suddenly disappeared from her app folder on her iMac! I'm not making this up. Both Macs? On the same day? After years of heavy daily use without ever seeing something like this?
Interestingly, Norton reported 3 viruses on my iMac: Backdoor.Trojan, W32.Mydoom.A@mm and O97M.Tristate.C . Not sure if any of these are relevant to the issue at hand.
P.