Well designed NPCs and factions have real motivations and modes of operation. Filing serial numbers off complex NPCs and organizations should never be that easy, IMO, otherwise your NPC or organization was so generic as to be meaningless anyway. An adventure in Waterdeep and in Sharn can certainly have the same plot, but it is the details that matter.
This is actually an area where some of the older, generic adventures were more interchangeable. The original ToEE was certainly set in the Flaeness, but it wasn't really
anchored there and could be run in any home brew setting with little issue. When you put the adventure into locations with notable features and ascribing motivations to certain named groups, it becomes harder. Not impossible (usually), but harder.
Princes of the Apocalypse was remote enough that it wasn't a big deal. Sure, the weird stone bridge needed to be replaced, but that wasn't horrible. Otherwise, I flipped east and west on the maps and swapped out names of the "off the map" cities.
Hoard of the Dragon Queen was a lot harder, though. There really isn't a good alternative to Baldur's Gate without pretty much rewriting that chapter and keeping just the high-level "make it hard to trail them". The cross-country merchant caravan was hard to replace because of the way House Orien maintains trade between major cities. I considered swapping it to an "Orient Express" type feel, which would have played awesome, but required a lot of rewrite. Looking at the first chapter of "Rise of Tiamat" is what really killed it for me, though. There just isn't an equivalent to the council you're supposed to plead your case to. The Twelve doesn't do that sort of thing. You could find a replacement, but it'd be more different than just "say it's these guys".
That's not to say that WotC shouldn't release setting-specific adventures. I absolutely think they should. At one time, I was hoping they'd bring back the older settings with some sort of cadence of "tightly coupled Realms adventure" -- "nominally Realms, generic adventure" -- "Ravenloft adventure" -- "tightly coupled Realms adventure" -- "Eberron adventure" -- "nominally Realms" -- "Dark Sun" -- "tightly Realms" -- "Dragonlance" -- "nominally Realms" -- "Planescape" -- etc. I was really looking forward to do a one-and done to
really experience each of the settings, even the Realms, in a sort of showcase tour of what made each great. At some point, I'm sure I would have wanted to go back to home brew or Eberron, but that would probably have held me for the better part of a decade and gotten me to buy half the adventures (we don't play as fast as some groups) and all the non-adventure material. Instead, I've given up on adventures and have gotten selective about the non-adventure material.
There are other release strategies that'd work, too. The point is, "just scrub off the serial numbers" doesn't actually work for everything.
