I'm looking for a secular alternative to the term cardinal sin as used to describe a significant act that goes against established knowledge, beliefs, and practices. Any ideas?
You might use violation or breach instead of sin. But outside of criminal law, where felony is distinguished from misdemeanour, we don't ordinarily rank violations, but qualify them ordinally: serious breach, gross violation. Instead, we rank the tenets or principles or practices which are violated; although you will encounter fundamental violation and similar phrases, these are elliptical for violation of the fundamental principle that ... or breach of the cardinal tenet, ....
You can easily avoid cardinal sin by instead referring to capital vices or mortal sin. You might also refer to heresy (“A controversial or unorthodox opinion held by a member of a group...”); for example, “Breaking compatibility is heresy/heretical”.
Regarding previously-mentioned taboo, whose senses include “An inhibition or ban that results from social custom or emotional aversion” as a noun and “Excluded or forbidden from use, approach or mention” as an adjective, and faux pas (“A blunder (especially used in social contexts); a misstep”), you can suggest more severity via adjectives like unbreakable and unpardonable (ie unbreakable taboo, unpardonable faux pas). Note, the synonyms gaffe (“A foolish and embarrassing error, especially one made in public”), blunder (“A clumsy or embarrassing mistake”), and misstep might also work.