If you modify .htaccess, you will have to maintain your changes through every core upgrade. There is no compelling reason to modify .htaccess. PHP configuration is better done with php.ini and errors in vhost configuration are better fixed in Apache.
Drupal 6 will configure sites/default/settings.php on initial installation. If you get your database configuration right at that point in time, you are set unless you muck with your database. Don't do that either.
There is no compelling reason to muck with $base_url or $cookie_domain either. A proper vhost configuration makes these configurations moot.
But as I said before - don't.