I run a multi-site drupal installation. One of the sites has civicrm installed on it, and works fine. Other sites do not have the civicrm module enabled and do not have the civicrm database mods made to their databases.
On the non-civicrm-enabled sites, I see warnings when visiting the admin->modules screen:
- warning: main(sites/cyclingsisters.org/civicrm.settings.php) [function.main]: failed to open stream: No such file or directory in /var/www/westgate/modules/contrib/civicrm/drupal/civicrm.module on line 34.
- warning: main() [function.include]: Failed opening 'sites/cyclingsisters.org/civicrm.settings.php' for inclusion (include_path='.:/usr/share/pear') in /var/www/westgate/modules/contrib/civicrm/drupal/civicrm.module on line 34.
I see no hinderance to functionality. It's merely an annoyance.