If Open Cities was the default, it would have taken twice as long to debug and QA. What would stop an essential NPC from wandering off into the wilderness and get killed by wild animals if some unforeseen event clashed with their pathfinding?
Open Cities being a mod is inconsequential to the fact that having one large map without cells to divide the various parts would result in far more interactions and bugs.
Essential NPCs are flagged to not die. Cities already have things like vampire and dragon attack random events, and NPCS have dispositions for what to do in combat e.g. flee to their home. Some won't die in NPC combat, only to the player hand. (IIRC)
You also have smaller towns that are entirely in the Skyrim/main world space and are subject to the same things you say should be an issue, so whatever design they already use works. NPCs can chase you through doors but like to return home already, too. Whether they're leash points or something else, the answer to what would stop that exists already and is already used.
The game is already in cells that are loaded and unloaded based on which cell the player is in. Open Cities doesn't change that, it just places the previously locked away worlds paces back in the main world space and moves NPC data over to the new version of the cities.
If you just run Open Cities and not other conflicting mods it works just fine. I had an OC centric mod list and even had it working with Legacy of the Dragonborn. It works just fine with regards to the main game, and any issues are from it being a mod and not because of NPC issues it causes.
I'm not convinced it would have led to substantially more bugs and testing. All of the affected cities are already designed to function in the world space, they're just cut and pasted into separate ones. They all have large walls to stop outside interference and guards along the long run up to the main gate. Beth already did the work.
I still see no good reason beyond technical limitations of the time that Skyrim (e.g. PS3 RAM) didn't have all cities in the main world space. As for why they didn't change that for F4 or SF is not something I can answer and I haven't played SF, but I know they if aren't changing it it for TES6 they're in trouble. Let's hope Starfield was enough of a kick up the arse.
If you haven't played Skyrim with OC, it's brilliant. It fits perfectly to open Whiterun's door for the first time and have the city just be there. If it was compatible with more mods I'd have been running it forever.