Using an well known setting is shorthand between the DM and the players at their table. If I want to run Dark Sun, that conjures up to anyone who knows the setting visions of the Sorcerer-Kings, of oppression, slavery, and secret rebels, of deserts, of psionics.
Taking a well known setting and tossing out parts and changing parts not only loses all that, but actively can confuse players expecting staples of the setting. "Waterdeep? Nah, I don't have any big cities in my Forgotten Realms - it's my setting to do with it what I will".
By all means make up a homebrew - that's what I do for every campaign I run. But mucking heavily with a well known setting is just asking for the DM and the players to be out of alignment about it. And that's a lot more work for the DM, or just problems ongoing in the campaign.
So sure, you
can change it however you want. Doesn't mean that doing so will improve the experience around the table.