Akismet will get pulled out, #19597.
Isolating the About strings is interesting, but how much are we really talking? Let's assume only about.php, credits.php, freedoms.php. What's our memory actually saved? I doubt much.
Removing the help strings would require a manual textdomain. And since help appears almost everywhere in the admin, it'd be loaded on every page. No huge benefit here. Ideas?
Splitting the admin and the frontend is worthy. We would need to load the admin textdomain in includes/admin.php if it isn't already loaded, in the case of including the admin includes bootstrap on the frontend (admin-ajax, just one core example).
I think the idea of tagging strings in is_multisite() branches with an explicit, manual textdomain is additionally intriguing.
Since this ticket proposes a number of ideas I am going to spin off the admin/frontend split and mark it as a task.