Simple. They all insist on their own particular brand of weirdness embedded in Apache. Whether it be loading a humungous module like mod_perl or mom_php; twiddling all kinds of security settings; or even just setting up a few virtual directories - all these fail because I am lazy. I prefer simple self-contained applications like the Prayer webmail system. I like it because it doesn't require any effort to get running. It just works. And it is independent of my Apache installation. That it happens to be written in C and so is bastard fast and consumes half of fuck-all memory is also nice, but I could live with something similar in less efficient languages like perl, python or even java.
However you do it, either having one ginormous Apache instance for everything, or lots of different instances with different configurations, there are big downsides - either you run out of memory immediately, or you have administrative headaches.
It seems to me that web applications written in perl are particularly bad offenders in this respect - almost all either require mod_perl or are horribly crippled when run as CGIs with virtually no documentation for this configuration. It can't be hard for application writers to fix this.