OK, I see what you mean now. Basically, you need to write some more code!
After you save the data from the meta box (presumably on the save_post hook), look for a matching image, check the correct sized version exists, and add it to (or replace) the post as the featured image.
Basically automating what would be done by hand.
Note: if you want to make these changes in the save_post hook, and it involves modifying the post record itself, you must use the database directly (but still via the DB API), you cannot use wp_update_post()! The save_post hook is called near the end of wp_insert_post(), which is called by wp_update_post(), so your hook will get called again and you'll be in an endless loop. Been there, done that, killed apache! If the modifications only involve meta data, you are good to go.
An alternative is to use the wp_insert_post hook, which is called after save_post.
Mike