I don't see "the scope needs to be big" as a battle, I just see it as kind of a constraint on what D&D-as-tragedy can look like. D&D's got big scope, and I'm OK with the scope of this tragedy being big (while still being related to the characters' own flaws).
And I'm very much interested in D&D-as-tragedy. I'm happy to loot ideas from other games (and somewhat expecting to), but part of the fun here is in defying the usual tropes of the heroic fantasy genre, and in playing an ongoing campaign like this.
I do think that one of the things to maybe loot from other systems is the idea of shifting narrative control. 10 Candles' shrinking dice pool is fun. And, it might be a good idea to set the stakes and nature of the big tragedy up front as 10 Candles does. Heck, the world-shaking nature of it sets this up nicely: The world is ending, and its your fault. There are heroes of destiny, and then there is the other side of the coin: grim reapers of worlds, destined destroyers. You're one of 'em. When the campaign is over, the world ends. You can't stop it. You can pursue your own goal within that bound. Do you seek to understand why the world is ending? To escape it? To save who you can? To revel in its final days? To delay it as long as possible? If I define that as the space of narrative control and use the shrinking dice pool, that could be a nice looting.
That might even work for the "NPC's do a tragic thing in an adventure, how do we make sure the PC's don't keep stopping it" example.
Like:
Premise: Say, 1st level. A Bonnie and Clyde quest where the PC's are chasing a couple of doomed criminals. Basic set up is basic D&D: they stole something, somebody wants it back, find them and get it. Moment-to-moment play is basic D&D: going to places, investigating things, fighting off bandits working for the couple, following a McGuffin trail to a hideout, delving into the hideout, etc.
Setting Up the Fall: Early on, first place they check, the party learns from others/diaries/etc. that the couple is wildly in love and willing to risk it all for each other. Plant this clue in plenty of places. Once I introduce the hamartia, I set down two d20's. I declare the outcome, something cryptic like, "This is fated: These two people will be each others' undoing."
Entropy: As a DM, I know I'm working toward a climax where they die in a conflict with local guards, with the PC's present for this. I imagine three key points on the journey from hook to that climax: 1) PC's find Bonnie and Clyde and find out why they're doing this ("One last big heist and then we can retire."), and then the pair escapes; 2) The PC's find them again, stop the big heist, and learn something about how this will play out ("They'll never take us apart! We're gonna have a big wedding when we're in the next kingdom!"), only to have them flee when the town guards show up; 3) The final stand, the town guards open fire, the PC's watch the two of them get riddled with arrows or fall off a cliff or get lit on fire or gut themselves with their swords or whatever. This happens while the party's busy with the thing they're actually expected to win against (the bandit captain, Bonnie & Clyde's second-in-command). The party gets a small reward for helping to end their reign of terror.
For beat 1 and beat 2, when I take control, I give a PC one of the d20's and say something like: "The pair escapes. Tell me how." That PC then has Inspiration to spend for the rest of the session.
Campaign Scope: Between the sessions, I describe how the world slips closer to demise thanks to something that happened in the previous session, something that arose from one of the PC's own hamartia in the session ("See, your character would also Do Anything For The Person You Love, and so when they asked what the guards did with the magical McGuffin Bonnie & Clyde were trying to escape with, you didn't withhold, though you maybe felt like your lover was a little too excited to learn that it wound up with that drunk, Sarge McGill"). I then give the party their nightmare about the forthcoming apocalypse and ask them the usual D&D question: What do you do about it?
And from there, we hook into the next adventure.
And probably not every adventure follows this format, but "give a PC a d20 for Inspiration and ask them what happens" while watching the resources dwindle...it retains player agency, asks them to conspire in the premise of the campaign, and gives them a little treat for helping out.
This is just spontaneous, I'm sure there's some refinement that I could do here, but this isn't....fundamentally alien to D&D. Most of the game plays normal, sometimes I just bribe a player to tell me how everything goes pear-shaped.