I'm very hopeful for Letters, a project just taking off under the leadership of some pretty big names: Gruber, Rands, Brent Simmons. They're hoping to collectively create a "lean and programmable IMAP email client, with plugin and automation APIs, designed for developers and power users." While still sparse and very early-stage, their vision document is ambitious: http://pastie.org/785269 If something comes from this, it'll definitely be a step forward to modernize email clients.
Project wiki: http://letters-wiki.heroku.com/