I've found it doesn't matter what HTTPD server you use.
You need to use separate installations for the Wordpress for each domain or sub domain. That way its able to be updated automatically by the users of the site... and make WordPress self updating.
Otherwise you'll step on everything "custom" and you'll be stuck updating from the repositories, while you'll be suck waiting for that when a zero day exploit comes along. Since its PHP and its an Application... its not very good combo.
Use a single HTTPD server (nginx or apache or whatever) with vhosts... and then separate installations of WordPress and then MySQL/Postgres.
Careful on the MySQL/Postgres stuff, since there have been specific exploit for PHP4+WP+certain versions of MySQL and PHP5+WP+certain versions of MySQL.