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When using the API, how does one handle the cases where a user in our database changes their email address? Given the email address is the only API identifier. If the API allowed us to query a list and return all emails, we could do this, but that functionality currently doesn't exist. Or if we could change the API identifier to one of our custom field for the user, their "personID", that would help too. Any customization that would allow that?
Yes the ‘email address’ is the only unique identifier.
If you want to change the email address, you’d need to 'unsubscribe' it, then 'subscribe' the new email address.