I'd wager any mbox optimization efforts are put on the back burner in lieu of modern usages, which seem to be in favor using it as a IMAP client only.
Having said that, i use mu4e these days, because i've become an Emacs user. With a few tweaks it now scratches my itch very effectively (except of course the HTML-email problem as mentioned elsewhere -- this is especially troublesome at work where they want me to include an HTML-embedded-image-tabled monstrosity with about a page of legalese as a signature).
That said there is an obvious solution to slow MBOX folders, which wouldbe to switch to using Maildir-storage, then using the `header_cache` setting(s).