I use Horde/Imp on a day-to-day basis because I can use it from anywhere and it has nice GPG/S\MIME integration.
If I'm dealing with larger folders (50k+ messages) I prefer Thunderbird and the threaded display option. Again GPG Integration (using enigmail) is of key importance.
I also need to be able to alter my from-address at will since I use different aliases for different purposes..thats why I never bothered with mail.app.
In addition mail.app does not give me any progress report when opening a folder, so there is no way to know whether the connection is just slow or broken just by looking at the app.

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"I also need to be able to alter my from-address at will since I use different aliases for different purposes..thats why I never bothered with mail.app."

Apple Mail can do this. Mail > Preferences >Accounts > Account Information just add the extra email addresses on to the 'email address' line, separated by commas. They'll be available the next time you compose/reply in a drop down box (copied from http://discussions.apple.com/message.jspa?messageID=2112595).

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