'--with-openssl' purpose is to override the OpenSSL location for Python's internal _ssl and _hashlib module. It is not designed to interfere with 3rd party extensions that are built with distutils or setuptools.

It is the decision of a 3rd party package how it wants to handle these extra flags -- or if it is able to use them at all. In case of PyMySQL you must use the same shared libraries as libmysqlclient. You cannot use a  different OpenSSL ABIs, APIs, or shared libraries for PyMySQL and libmysqlclient.