By default Mail.app imports all of your pre-existing sigs to all of your email addressess and signatures. This is a nice little touch, but it associates all of the addresses with all of the signatures. From this I realized that you can have multiple unique signatures that are associated only with certiain email addresses.
All you have to do is select the account that you would like to use and edit the signatures that are affiliated with that account. Then in the little drop-down list below the 3 panes (see image above) select which address you would like to appear as a default. Now create a new email and switch from account to account and watch the signature change based on what you selected. Repeat & enjoy. 😉
This is both cool and useful. As you can see I only have one sig assigned to my business account so that If I am sending an email on that account nothing foolish gets attached to the message.