Instead of using DefaultSettings.php to initialize a number of globals, the default values for all config variables should be loaded from config-schema.yaml.
However, since parsing YAML is comparatively slow, we may want to generate a PHP file that can make use of the opcode cache. That file would however return an array, it would not manipulate globals.
Generating that PHP file could be done by a maintenance script, and we could use a structure test to ensure that it is in sync with config-schema.yaml.
NOTE: Since developers often consult DefaultSettings.php for documentation of config variables, the file should be kept in place. It should contain only big comment explaining where to find documentations and how to add new config variables.