While it sounds quite nice in theory to slim down your configuration to only have runtime configuration for variables that you see yourself changing, what I imagine ends up happening in practice is that you're left in a situation where you're doing far more work and only superficially benefitting by having an config that appears short and simple, but is in reality a complex system with nooks and crannies.
Here are some problems that I see with this:
* You're now on the hook for maintaining this software. Security problem? Your problem. Update? Your date, canceled, because an upgrade to the program changed everything. The version distributed by your distro had a nice post-installation hook for the new layout, but you have no such benefit. Your distribution might even have a few distro-specific patches for the software. Is tracking the upstream version, tracking your distros patches, and compiling the software actually saving you effort?
* Potentially undefined behavior. A configuration option can be in undefined and taking a default value, defined at compile time, or defined at runtime. Are you intimate enough with this code to know what's going to happen when you define it in multiple places? Maybe you add something to your runtime options, only to find out a week later that the change never happened because it was already set at compile time and that takes preference. Maybe the program has a runtime exception and crashes 3 days later at 3:00AM because it doesn't know what to do when it finds it in multiple places.
* Who the hell is looking at their configuration options enough that this actually crosses their mind? I've configured exim4, so I know exactly the situation you're describing with regard to a configuration that is just downright ugly. But I don't have a visceral reaction because I know that once I've configured this, I'm done. Maybe a few months later I change an option.
Mixing compile time and runtime configuration means you not only lose the advantages of both, but you gain their disadvantages as well.