Whenever possible I use gnus, primarily for the newsgroup-thread-style UI and editing power of emacs. I also take advantage of its inherent customizability with elisp to handle my different From addresses, conditional BCC, filtering, etc.

I use gmail for low priority traffic like mailing lists, and everything else goes through FastMail (http://fastmail.fm/) which is quite simply the best email host I've ever found. For $40/y you get hosting for 50 domains (and 30 aliases on FM's many domains); SpamAssassin; Sieve filtering; secure IMAP, POP and SMTP; 2GB storage; and a nice web UI which suffices when I'm away from gnus.