Flaviviruses are small RNA viruses that exhibit genetic and ecological diversity and a wide range of G+C content (GC%). We discovered that, amongst flaviviruses, the GC% of nucleotides encoding conserved amino acid (AA) residues was consistently higher than that of nucleotides encoding variable AAs. This intriguing phenomenon was also identified for a wide range of other viruses, and some non-viral evolutionary groups. Here, we analyse the possible mechanisms underlying this imbalanced nucleotide content (in particular the role of the specific G content and the AA composition in flaviviral genomes) and discuss its evolutionary implications. Our findings suggest that one of the most simple characteristics of the genetic code (i.e., the G or G+C content of codons) is linked with the evolutionary behavior of the corresponding encoded AAs.