ITunes Suddenly Malfunctioning Strangely & Randomly - Hard to Describe

Question

In the last few days, my iTunes that has been stable as a rock has started malfunctioning randomly and strangely. It's one of those situations where it's fine for a while and then silently craps out with no apparent cause.
The first telltale sign is that my Podcasts list will suddenly have an gray exclamation point next to every single entry - same as a failed update when a remote server related to a given podcast is down, except it's every single item. It's as if iTunes has fallen off the network, but the machine is fine and has never lost a connection.
When it's in this state, my iPhone will also fail to sync with any of several different error messages (one involves being unable to read or write from disk, etc). My AppleTV might also be inaccessible - I've not thought to check for certain.
A number of times in this state, hitting Apple-Q was also totally ignored. I have to select Quit from the File menu with the mouse. Any number of other things in iTunes behave oddly, too.
If I do quit and immediately restart it, though, it comes back with no complaints and functions fine in every way. Syncs, podcasts update, etc. Turn your head for a bit and next time I check, odds are good it's out to lunch again as described above.
The issue is so broad across its various behaviors with such a mix of error messages that I've not yet spotted a pattern. I don't know whether to say its related to interaction with my AppleTV or iPhone, something network related... it all has me pretty perplexed.
Anyone else seen something similar? Whatever the case, I can pretty much rely on it happening again any minute now. I'll try to be more systematic in what I poke and prod each time until I can zero in on a pattern.
- Aaron

Answer 1

I've had two more instances of what I described above in the last couple of hours. This time I ran into it before the Podcasts had a chance to all fail. Apparently they hadn't tried to do a scheduled update since whatever happens happened, but clicking refresh causes them all to fail and results in the exclamation points mentioned above.
In addition, re-docking my iPhone resulted in some message about possibly having too many files open. Hitting sync a second time resulted in a different message about the disc not being found. Then another message about not being able to read or write to the disk. Blah blah blah.
I clicked on my AppleTV and then hit its sync button. No errors. It just vanished completely from the Devices list as if it had never been there.
No file I double-click will play.
So far, these are all the things I've experienced in previous incarnations of this problem.
iTunes is also not responding to Apple-Q to quit when it's the active app. I need to use the File menu with the mouse to get it to quit.
Once I restart it, all will be well until it happens again.
I don't see any hung processes in the Activity Monitor including iTunes. Everything seems fine, except iTunes is "doing it again".
No, I don't need repair file permissions. Did that earlier (and, frankly, I find that to be voodoo more often than not).
Anyone else?
- Aaron