You could use the different "pages" of the action bar. So page 1 has buttons with "follow A", "/cast [target=A-target] ..." and page 2 has "follow B" and so on. Instead of shifting focus to set a new leader, you would flip action bar page.

The two problems are 1) it takes a lot of macros, and 2) it takes a very long time to set up, test and change all those macros.

Those problems can probably be solved. I have heard trinitybars can handle unlimited macros for instance. And there are API functions for editing macros, so you could make an addon to create the macros in bulk from a template.

But is it really worth it? :P

edit: Thinus had a good idea just above. You could have your spells something like this:
Code:
/click [noharm][noexists][dead] ActionButton12
/cast Fireball
Now on each action page you have identical macros, except the last one, Action Button 12, where you have different assist macros. The biggest problem here I think is just that you have to push twice to cast a spell whenever you target a new mob. It will still take a while to setup, but you won't have as many macros to maintain.

Your assist macros are just "/assist A", "/assist B" and so on,
and to set your assist you can use keybindings for setting "Action
Page" or possibly even "Next/Previous Action Bar", saving macro space.