How to optimize an application articles are usually deserving of the scrutiny they receive but this tip on making the Apple mail client faster really made quite a bit of difference for me. Mail actually feels responsive now and initially loads in a couple of seconds rather than the 20-30 second delay I've grown accustomed to.
Here is my net loss:
Before: 1 goneaway goneaway 110M Mar 2 04:30 /Users/goneaway/Library/Mail/Envelope Index
After: 1 goneaway goneaway 21M Mar 2 05:13 /Users/goneaway/Library/Mail/Envelope Index