The hunt for complex organic molecules (COMs) is a major concern for understanding the possible role of interstellar chemistry in the synthesis of the molecules that ultimately may be at the origin of life. A comprehensive screening of the 14 species effectively observed under 32 different isomeric forms in the interstellar medium has been done by means of high-level quantum chemical simulations. Confrontation between calculations and observations shows that when several isomers of the same generic formula are identified, it is always the most stable one that is the most abundant. Moreover, the abundance ratio of the most stable isomer to the other isomers is directly related to their energy difference. What can be seen as a minimum energy principle is verified in molecular clouds, hot cores/corinos, photodissociation regions, and asymptotic giant branch stars. The few exceptions encountered could be rationalized either by the existence of different routes of formation with no intermediate in common and/or specific depletion on the grains of one isomer with respect to the others.