Good Omens features a central, deeply implied queer romance between the angel Aziraphale and the demon Crowley. Their centuries-long, co-dependent relationship is portrayed with dignity and complexity, serving as a primary narrative driver. The show affirms their bond as a positive, world-saving force, free from harmful stereotypes or negative framing.

The series features gender swaps for several characters from the source novel. Pollution, described as male in the book, is portrayed as female. Beelzebub, generally referred to with male pronouns in the book, is also portrayed as female. Additionally, the voice of God, traditionally understood as male, is portrayed by a female actor.

The film satirizes the rigid, bureaucratic, and often destructive nature of Heaven and Hell, which represent institutionalized divine authority within a Christian-derived cosmology. It portrays angels and demons as largely uncaring or actively harmful, prioritizing a 'Great Plan' over humanity, thereby critiquing blind faith and dogma.