I ran "qmail" for ~2 million mailboxes, and the greatest appeal with qmail was that the design made it trivial to replace anything. Hence the quotes. We started out with near-pure qmail, and ended up replacing or modifying component by component because there was a well-defined API between each piece.

Spam was never the issue for us - tieing things in with filtering was not a problem. I think the bigger problem for qmail was that because of the licensing, you pretty much had to patch qmail, which meant you needed developers happy to effectively maintain your own version or at least patch sets. If you were building your own mail infrastructure (we were - we ran a webmail provider until we sold of that bit), that was fine and it was a good scaffold while you customised what you needed, but if you just wanted to run a mail server and it wasn't your core business it very quickly stopped making sense to deal with that hassle.

It's a real shame, but a good example of how license choice can affect things...