For reasons I can't remember (!), we need to make a Pier  
installation act at the top of the domain.
So instead of:
www.domain.com/seaside/path
we need:
www.domain.com/
only.

How can this be done?
    

1. set the base-path of the application in the Seaside configuration  
interface to /

2. use Apache 2 to become a proxy for Squeak running on Port 8080

<VirtualHost www.domain.com:80>
   RewriteEngine On
   RewriteRule ^(.*)$ http://localhost:8080/seaside/pier/$1 [P,L]
</VirtualHost>

This is (more or less) the configuration I am successfully using for  
several Pier instances.

Other possibilites have been discussed in length on the Seaside  
mailing-list, so you might want to check out the archives there.