I recommend Mozilla Thunderbird + Markdown Here add-on.
Mozilla Thunderbird is, of course, an open-source, cross platform e-mail client that is extendable with add-ons (plugins).
When you install the Markdown Here add-on, you will get a new toolbar button labeled "MD Toggle" on your message composition window. (Note: after you install, you may have to right-click the toolbar, select Customize, and manually add the button to your toolbar before you will see it.) You can then type your message in markdown, and click the "MD Toggle" button (or Ctrl-Alt-M) to toggle back and forth between markdown code and rendered output. It works very well.
It also supports GitHub style code syntax highlighting and TeX mathematical formulas.
The advanced options are nice too, as you can alter the CSS rules used in the markdown rendering, if you like.
By the way, if you want to use this with your favorite webmail provider, Markdown Here is also available as a plugin for Firefox, Chrome, or Safari.
