I don't feel constrained by D&D's wider canon at all. Most of what hasn't been stripped comes from Planescape and Greyhawk, neither of which I much like, while the Spelljammer canon was unceremoniously swept under the rug.
Even for settings I like, I don't feel constrained by canon in the least. Even most of the Spelljammer campaigns I've run were set years after the events described in the boxed sets, novels and published adventures, so I could set up the political situation as I liked and have intra-Sphere politics impact groundling politics more directly.
Exception: When basing a game on an existing property (a Final Fantasy game, say, or Star Wars), I'll either keep everything explicitly stated in the source material, explicitly call the campaign out as being alternate reality, or explicitly make the changed elements something that was subjective (and wrong) on the part of the character who stated it in the source material.
For example, if I did an FF7-based campaign, I might change the nature of the lifestream from a natural 'river of souls/cycle of life' to an artificial engine for draining ambient magical power - but if I did, I would make it clear that Bugenhagen was lying about it and Aeris deceived, and make that a plot point. I wouldn't just make the change without explaining it.