It's common for enterprises and hosting providers to have an unnecessarily complex and inefficient e-mail handling, because the system has grown over time. There might be many back-end mail servers, many layers of filtering and routing, and each one of these performs store-and-forward e-mail routing (because that's how e-mail servers work). However, as soon as one system as accepted (stored) the e-mail from the sender, its no longer possible to reject it, or perform other error handling without creating DSNs (or NDRs), which are a problem of themselves.
Ideally, there should be only one, seemingly transparent, e-mail routing and spam filtering layer in front of the e-mail servers. In that way, even the back-end e-mail server can reject or defer a message (because of blacklisting, non-existing users, full mail boxes, etc). Routing should be dynamic, not requiring any per-customer or per-server configuration or maintenance.
Meet Halon Security's SPG/VSP e-mail security gateway. It's transparent in the sense that it performs all handling and routing in-line; that is, while receiving the message (during MAIL FROM/RCPT TO/DATA). It has an extensive scripting language which enables you to produce extremely elegant and dynamic configurations, where everything is resolved dynamically.