Much as one is more than the sum of their arms, legs, heart, and brain, so too is a house more than the sum of its parts. Everything is connected in both "systems," and often in unexpected ways!
Having a dark roof will make air conditioning bills higher. Putting in a beefier kitchen exhaust fan can starve a distant water heater of air and cause dangerous pollutants to flow down (rather than up) the flu or make a fireplace dump smoke into the living room.
There are often tell-tale signs when a home is not properly acting like the system it was intended to be. For example, ice dams are evidence of excessive heat loss, which make pretty icicles on the eve but can cause severe roof damage and danger on the ground. Moisture damage or bad indoor air quality are usually dead giveaways of some deeper problem (or multiple problems!).
The art of bringing a home back into "balance" frequently involves finding sources of air leakage. Often, an important (but out of sight) location of leaks is in the heating and cooling ducts. Providing enough air for combustion equipment like furnaces, water heaters, and gas dryers is also crucial. Tools like blower doors can be used in worst-case tests to see how the home system performs when stressed.
The story of a home-as-system is also told through the many benefits (in addition to energy savings) that can be had by fixing performance problems. These take the form of a quieter living environment, higher comfort, and elimination of safety hazards.