Mozilla Thunderbird is my day in, day out favorite email client. When most people think about email, they think Outlook. Outlook is a great program, but it's very expensive. Unless you need to connect to an Exchange server, you can do better with the free Thunderbird.
I've finally untethered my iPhone from iTunes, at least for keeping my calendar and contacts up to date. I'm using Thunderbird to manage email, contacts, and calendar, and using Google as a back end to keep it all synchronized between the iPhone, my Linux desktop, my Windows Vista notebook, and Google Apps on the web.
Mozilla Thunderbird