I use Gmail on the web. No local client. (This is probably the biggest saver! Deleting my local mail from my computer saved me about 6 Gigs of space.)
I use keyboard shortcuts and the "To" and "Cc" indicators (The little >> and > signs)
All listservers skip the inbox and go straight to their labels.
All "bulk" email (twitter and facebook notifications, marketing emails, advertisements, special deals on Hertz rental cars, etc) is tagged as "Bulk" and skips the inbox.
For the periodic "checking" of email I use Google's Notifier application. (http://toolbar.google.com/gmail-helper/notifier_mac.html) Where I have shut off the sounds, and shut off the popups.
This also has the added benefit of working with my Google Calendar, where I DO have pop-ups enabled to remind me of stuff.
I process email to Inbox Zero everytime.
To flag emails I use the little stars.
To make To-Do's I use Omnifocus. This has the added benefit of, you know, in case Gmail goes down (as it has recently a couple times), your "To-Dos" aren't managed by your Inbox.
This has made my email process so efficient, I don't have to waste time screwing around with how to make it "Better".
I thought about using tags to flag things as "To-Do" or "Important" or "Needs to be done" or something. But I don't want to mess with my system. It works.
Please leave comments below.