Not sure if most of the switching is between email accounts, but if it is, I've been using the 30 day free trial for MailPlane (http://mailplaneapp.com) and have been pleased with it.
I'm going to pay for it when the trial is over ($24.95).
I have an ssd so the speed isn't a concern for me, but as osx lacks trim support, I am concerned about huge caches.
Have you seen or noticed the cache being overly large?
I have a lot of e-mail and 'labels' and I seem to do just fine.
TRIM support is coming in Lion (OS X 10.7) but I am sure you know that since you know 10.6 doesn't have it. I still felt compelled to type it though...