Well what I consider cannon I take from the Fallouts as well as the Bibles, although I do not know if that is generally considered part of the cannon by the community. What they break: Reason for Enclave being there, Reason for BoS being there. FEV has changed. Vault 67 is a huge cannon breaker. Super Mutants aren't the same brand as west coast. Deathclaws somehow in the East, even though they are mutated desert lizards. Dumbing down the use of the G.E.C.K. Ghouls no longer caused by mix of FEV and radiation, just radiation now,etc. Alot of the more damaging ones, IMO, are spoilers and crucial to the story, so I shall leave you to find them yourself.