A great example, for me, is the Arkham game series. I've enjoyed each game, but as the 100% completion has gotten bigger and bigger, finishing the games has gotten more and more tedious and less fun and engaging. The depth of the gameplay doesn't last long enough.

Ah, so its long, but lacks the depth to keep you from getting bored before you reach the end.

All games get old sooner or later. The less there is to them, the sooner it happens. Different levels of complexity call for different lengths of game - for storyline based games that have a specific end - unless the story itself is enough to keep the player engaged. For open ended games, you just play until you get tired of it, or retire that game and start a new game.

With storyline based games its extra tricky. You're mixing two types of entertainment in one product: storytelling, and game playing. Each will have its own "opinion" about how long the game should be. If the story demands a long game, the gameplay must have the depth for a game of such length. And visa versa. The story should be engaging enough to last until all game play has been exhausted / thoroughly explored. I think skyrim might be an example where the questlines don't quite stack up to the sheer volume of gameplay. OTOH, skyrim also has a distinct "more of the same" type design to it. Its really big claim to fame is that it has so MUCH more content than most games. I still find new content from time to time while playing it, and i probably have over 1000 hours in the game with all the characters i've tried. TES and the sims are the two games that influence Caveman, so when Skyrim came out, i had to check out the ENTIRE game. It took something like 8 characters to do it (one for each major questline), at a couple hundred hours gameplay each.

one way (using instances) where other non-designated players are prevented from interfering and constantly making a hash of any planned (choreographed/designed/coordinated) sequence of interaction with npcs/terrain for the Mission the player has been told to do.

This is just making a single-player game inside an MMO lobby, it's not a real MMO (while almost all of modern "mmo" games doing this). I'm going to make a real MMO, where players could always interact between themselves.

And all described issues are not isseus, in fact. It's a part of MMO experience (with correct game design).

Its a matter of degree. You would allow prearranged 'party' (people you invite to take part) to play through the protected mission. Unfortunately there are MANY dimwits out their who gleefully will ruin the activities of every player they encounter and generally it is utterly simple for them to do it. (while you advance your character to Play, THEY figure out every shortcut/optomization to find ways to either kill you instantly (ganging up is so easy for this) or to disrupt any mission situation so that you will want to quit in disgust)

Dont count on Gamemaster intervention for any of your 'correct game design' to solve this as it is $$$ prohibitive. Even with automatic evidence recorders and complaint submission and banning, the labor expenses will largely invalidate such measures. Draconian Automatic mechanisms are required and unless being something as simple/absolute as blocking interaction or isolation THOSE themselves usually wind up being subverted for griefing activities )

forcing you into very simple 'mission' goals and actions

Still don't see any reason why it's forcing to a simple quests. The quests could be as complex as it's required for the game, just they should be designed for a multiplayer game, not for a single game.

Because your efforts to provide anything intricate or interesting will simply be attacked by asshole griefers (you try fighting a more than one-dimensional boss challenge (a close fight) when a (PvP enabled) griefer is ready to zap and kill you at the right moment. (and who will make it THEIR mission to ruin the situation/game for you). Thus all missions have to be utterly simple (braindead) and over quickly and unchallenging (and generic and numerous and unrewarding) so you can finish them before the assholes have a chance to interfere. They learned this about 20 years ago with the first MMORPGs