I had also been on witch hunt for quite some time to fight off the spinning disk of death... and in the end, spotlight was the culprit.
1. While I'm sure that chipping away at potentials has helped, ultimately putting my photos (why index files named DSC232122?!) and emails (I search those in mail... not spotlight) onto the private list for spotlight fixed a 5 month long saga of angst and rage at my poor MacBook pro which I purchased full loaded less than a year ago and was becoming unusable.
I mention these two folders here as good candidates to exclude because in my case:
Usr/Pictures: 39GB in 1,227 items
Usr/Library/Mail: 24GB in 152,215 items
As you can imagine, when spotlight stupidly started indexing while I was clearly using the machine... it became unusable and I... well... @^#%*!%!!!!
2. I also then came across this neat post in which the user suggests that deletion of your old spotlight index results in more processor efficient indexing:
Ideally, I wish that OSX would at least wait until the machine was not in use by a human for X amount of time before initiating is spotlight index rebuild... and even then, limit how much processing power it's allowed to hog!