Guys not sure how much this helps, but I have found the two biggest culprits are:
1) and I really feel this is the biggest one, is the power settings for your hard drive. I have just tweaked mine to not turn off the hd for 2 hours and am yet waiting to see the "not responding", If I don't see it for 2 hours I will set it to never, and never look back. Yes I have a sH@tload of apps open to test this theory.
2) I run Norton endpoint security, and noticed turning off the active scan from the default to once a day reduces this greatly, before I think the default runs hourly, it would interrupt movies as I was watching them. Currently I have turned this on to run every 10 minutes so I can rule this out over the HD going to sleep.
It has been over 10 minutes and I have yet to see my friend "Not Responding" and all the usual suspects have been running and then some. Yes I added photoshop in there too to really test this.
I will post tomorrow to update if this fixed it.