I'm using a rmail+m{pop,smtp}+mairix+spamassassin approach nowadays (My email provider's spam filtering is crap, so I do it myself, with a whitelist from my BBDB). Notmuch always seemed interesting but I couldn't dive in yet. I have some free time this week, so I'll try. If your configuration is public (i.e. on github), would you mind sharing a link?