1 and 1
I've always liked 1 and 1 (http://www.1and1.com)
I'm currently hosting over 100 domains with them and have had more than that over the years.
Domains are inexpensive and I can actually get a live person when I call customer service. I don't think I've had to wait on hold more than about 20min-30min in peak times and most of the time my wait is less than 10min.
Their online help is decent and once you've done something once on the site its pretty straight forward.
For something like $10-$20/mo you can host A LOT of domains on a single account with them.
As for email...
They do have an email interface but their web email leaves a little to be desired. I'd recommend using something like Postbox, Thunderbird, etc as an external mail client OR (depending on your size) use Google apps for domains.