Change default Safari email client to Gmail
Update (2016): find up-to-date advice in this question on Ask Different: How can I use Gmail as the default mail client app in Mac OS X?
The remainder of this answer (written in 2009) is obsolete, as Google Notifier for Mac is no longer supported.
Here's one way:
- Install Google Notifier for Mac
- Open Mail.app, go to Preferences -> General, and set "Default email reader" to Google Notifier.app. (Yes, you need to set this in Mail even if you don't want to use Mail...)
Works great for me. And in general I can vouch for Google Notifier too. It's a nice little app that adds an icon (like this: 
) in the menu bar and notifies you (if configured to do so) about new mail in your Gmail box.
GmailTo
Gmailto No. 2 is a little app that allows you to set Gmail as your default email client in Mail.app, so that any email link you click opens a new email in Gmail’s web-based interface.
Download it, put it wherever you like and then open Apple Mail’s General Preferences. Select Gmailto (2) from the list like this and you’re all done:
As you can see from the screenshot, two Gmail notification utilities — GmailStatus and GmailNotifier — allow you to do the same thing, but if you don’t want to use either of them, this little app will get the job done.
Edit: Apparently this app was created in 2004. I found a Greasemonkey alternative.
But I also found a mirror!
There is also a Safari extension (and Chrome extension) called mailto: which also offers the same functionality.
- Chrome: http://code.google.com/p/mailto-chromeextension/
- Safari: https://extensions.apple.com under Email (or direct install)
Unlike some of the other solutions posted here this still works as of 2013.