I think it really is all driven by personal preference. There is more great high end audio gear (components, speakers, cabling, accessories, etc.) out there right now than ever before in history. And so many different components from different manufacturers will work well together and will produce a certain type of sound. The question really boils down to which type of sound you prefer. What is highly detailed to me may sound etched and cold to someone else. What they consider warm and musical, I may think is overly euphonic and distorted with rolled off highs. And there are a million shades of gray in between all these extremes.
And it isn't just about the sound. We fall in love with components because of elegant design, sturdy build quality, and often times because of the pedigree of the manufacturer. All of these things influence how our systems come together. Ultimately, it is a lot of trial and error. We buy or borrow a product and try it in our systems. If we are happy with the result, we keep it and move on from there, looking for the next area to upgrade. Opinions from others certainly help us to understand the benefits, limitations, and house sound of a product. That is why forums such as this one are so useful.
I don't think there is a scientific framework to follow that will ensure system synergy, but I think there are always scientific principles to consider with each purchase that will help determine the ultimate outcome. For instance, there are valid scientific reasons why you don't want to pair a SET amp with an electrostatic speaker. Or why it is helpful to treat the room with bass traps and some absorption or diffusion behind a dipole speaker. Or why you don't want to use an ipod playing mp3s as your source.
But there are just too many variables to have an overall scientific framework. For every rule you tried to come up with, there would be ten exceptions.
Science is important every step of the way, but just as important is experience. Doing this as a hobby for years and years, you gain a lot of wisdom and experience that helps guide you toward finding the system synergy you are looking for. I have listened to a lot of different high end systems and each one is a completely different mix of components, but all the personal systems I have heard have sounded great. The only really bad sounding ones have been at the dealer showrooms. That's because people who care take the time and the effort to piece together a system that is more than the sum of its parts. That is what system synergy is all about.
For me, the key with building a system is starting with the best speakers you can afford, and then slowly upgrading each component in the chain above them -- first the amp, then the preamp, then the source, then the cables and accessories. This way you can really hear how each upgrade affects the sound coming out of the speakers and changes the overall synergy that you are trying for.