You’re probably already encouraging your clients to track their guestlist through some sort of spreadsheet or database. If you aren’t already doing it, make sure each guest (or guest unit – couple, family, etc) gets assigned a primary key (add a column and assign each row a unique number).
When sending invitations, pencil in the guest’s unique number on the back of the RSVP.
That way, even if a reply comes back illegible or incomplete, you’ll know whose response it is.