You can "force quit" an app several ways.
Control + Option + Esc on your keyboard
Or from your Apple menu > Force Quit
Or launch Activity Monitor located in /Applications Utilities
To avoid mail from freezing, try rebuiliding the mailbox.
From the Mail menu bar click Mailbox > Rebuild
And try deleting mail in the Trash and Junk mail folders more often.
Why is this still a problem 10-25-2012? I force quit and the dang thing still aborts shut down half the time.
Nothing in Trash Nothing in Junk. This is a user problem that APL is not addressing. Give us a way to kill the sucker.