Mail client locking up?
I would think a good way of doing this might be to package your ~/Library/Mail folder within an encrypted disk image.  As long as it was allowed to grow to an acceptable size, I think it would work.  You would need to move the Mail folder into the disk image, then create a link from your ~/Library folder, called Mail, to the "real" mail folder on the disk.

In order to get to your mail, (I imagine), firing up Mail.app would follow the link to the disk image, which would prompt for your password, as it needs to mount.

Once you're done with your mail, you would be able to dismount the disk image and voila.

Never having tried this, I have no idea if it would work.