as a general guideline, the character that requires the most micro-management should be your primary.

with a mage / priest combo this will depend on your play style, but there is no reason why you can't swap between them as needed.

set up autohotkey or keyclone as needed to pass the relevant keys to all your wow instances, download jdraughn's multiboxer mod (allows easy change of leadership and auto-follow among other things)

take a look at the macro's and addons section, there is some great info there.