I'm going to dive in here and give a huge thumbs up to mu4e. I spent a chunk of time with Gnus and Wanderlust and both feel so much slower. I can't make the switch yet because I'm too lazy to research how to get the multiple mailbox/index configuration I have with mutt (if it's possible?) but hopefully will soon.
There can be only one database (index) per mu4e/emacs instance, but you can store multiple maildirs in one database though, and there's support for multiple accounts (esp. in the upcoming 0.99; there are some recent ML-threads about this).
Really appreciate the work, djcb.