Entourage

From Applepedia

Microsoft Entourage 2004 offers a great deal of features for the power user such as hierarchical folders; integration with contact, task, note, and project managers; the ability to flexibily customize views, and much more. While the open-source Thunderbird is catching up, especially by its extensibility through "extensions", Entourage still has many features not yet possible with Thunderbird.

One well-developed feature is the integration of Entourage with Applescripts. Mail "Rules" can be added which, when certain conditions are met, will trigger an Applescript. Thus, for example, one could have a script turn up one's computer's speakers (or a remote ringer, such as is possible with the scriptable Indigo home automation software and corresponding hardware) and speak up that one has received mail from so-and-so, etc.