Sure. I'll try not to waffle too much, but here are six general pieces of advice I have for running serious games:

You Have to Set the Tone

This sounds really obvious, but it's the step that so many GMs miss. You can't assume your players are on the same page as you. If there's a tone you want from your game, you need to actually say that right from the start. Tell people what you want from them. Otherwise how can they deliver it? A great way to do this is to give points of reference. I often describe my games as "Serious, but more Firefly than Heat"; the characters make jokes as a way of dealing with their situation, but the situation is also very real and very serious. Joking about the bullet won't stop it from killing you. There's banter and fun and found family, but in the face of deadly threats. Try to find similar points of reference for your games. Are you looking for Michael Mann, or Guy Ritchie? Do you want deadly serious, or do you want "One of those surprisingly dark Saturday morning cartoons,"? There's a lot of different flavours of storytelling out there, so it helps to give your players the right idea going in. That way, if it's not for them, they can tell you right from the start instead of ending up at odds with the game because it's not what they wanted.

Session Zero is Essential

If you're not familiar with session zero, it's basically a thing you do before the game starts. It doesn't technically have to be separate session, but the point is that you should avoid the urge to just have everyone turn up with characters and start playing. Make character creation a collaborative event; you want your players to be having a conversation with you and each other about the kinds of characters they want to play, and the kinds of stories they want to tell. This is your opportunity to catch game breaking problems early. One player wants to be a vampire, another wants to be a vampire hunter? Have them talk it out. Figure out how this is going to become the kind of story that everyone will enjoy, or what alternatives can be explored if there isn't a good way to make that story work. This is also your opportunity to lay out the tone and feel of the game and have your players make characters that fit that tone. If you're running a serious game and one of your players wants to be Bimbo The Fart Gnome, this is your opportunity to simply say "No."

"Yes, and..." is For Comedy. Learn the Power of "No, but..."

The worst piece of advice ever given to new GMs is "Yes, and..." which is a technique from improv comedy. If you want improv comedy it's a great technique. If you want serious stories, it's a terrible technique. Instead, learn to say "No, but..." That means you can refuse things that will break your story, but you must always do so in a way that encourages and values the player's participation. In practice this means you need to offer them an alternative that carries the spirit of their idea into something workable. This doesn't even have to be obvious; sometimes it can just be a matter of reinterpreting the player's intent in a way that works. If your player says "I want to use my Intimidate skill to stare down the Mafia Don and make him do what I say," you can tell them to roll for it, and if they succeed, respond with "The Don laughs and slaps his thigh. 'Damn, you've got moxie kid. Tell you what...'" They don't give the character exactly what they want, because they're not intimidated, not even slightly, but they respect the spine they showed and warm up to them as a result. The player might have been entirely wrong about the amount of power they had in that situation, but they weren't made to look foolish. Their success mattered.

Consequences are Everything

The single most important part of running a serious game is that consequences have to matter. This is, I have to admit, part of why I don't try to run serious games in D&D, a system that is largely allergic to consequences, but that's beside the point. What matters is the choices your players make, good and bad, have to result in real, meaningful outcomes. This is why a lot of GMs fail at running serious games; they go in with a story in their head, and they try to railroad the players into that story, but by doing so they remove any meaningful consequence to the player's choices. The outcome will always be the same; the story will go in the direction the GM wants it to. Most players will respond to this by saying "Fuck it, might as well be silly, it doesn't matter anyway." If you want your players to care about the story, you have to make their choices important and meaningful, even when those choices fuck with your plans. One of the best endings I ever had to a game happened because my players wildly misinterpreted a situation; rather than try to disabuse them of that notion, I decided to simply accept their interpretation as correct and run with it. The result was an ending that had players in tears. Big dramatic character deaths, defiant last stands, moments of sacrifice that resolved campaign long personal arcs. All of that would have been for nothing if I'd stuck to my guns and told them that the threat they'd been trying to stop was actually a potential ally, as had been my original plan.

Use What the Players Give You

Listen to your players when they talk about their characters. When they bring up backstory, make suggestions, create connections with the world. Weave in those elements into your stories. If you take the things your players connect with and give them value, your players will be more connected to the story. This also comes back to your session zero; when you create characters, encourage your players to think about their connections to the world. Murder hobos are boring. Ask - demand even - that they come up with characters, places, ideals and things that their characters are passionate about. Things that matter to them. Then throw those same things in harms way and watch what happens. I guarantee you'll get a good story out of it.

Ground Your Players in The Story

The hardest part about running a serious game is that you have to respect that it's hard on the players too. Humour is easy. Tragedy requires us to be vulnerable. It's really challenging to put your heart on display in front of a group of people. So your players natural inclination will be to pull back, either by making jokes, or by making their characters too cool, too tough, too unaffected for it all to matter.

There is an incredible power in the words "How do they feel about that?" Ask it often. Start out a session by recapping what happened and then say "How are your characters feeling right now?" Ground your players in their character's thoughts and feelings, help them and encourage them to engage with the moment. If you feel like a character is reacting in a way that doesn't make sense or that feels like they're metagaming instead of flowing with the story, don't fight them on it, but try instead to explore it with them. If a player says "My character is too hardened and tough to care that those people died," let them run with that, but encourage them to explore it; What must it feel like to be so dead to the world that watching an entire village get massacred does nothing to them? How harrowing and haunting must it be to carry so many ghosts that a dozen more don't even move the needle? Respect their choices, but explore those choices. Help them to build out those roleplaying decisions into a fully fleshed out character.

And @Xaphanos@lemmy.world was never heard from again.

Of course. It's the most logical solution

I love this analogue but especailly because in play the players start trying to plan on mission impossible and then ends with Yakkity Sax because something went wrong. Or my favorite is the completly finished heist without any problems and just before they leave they go YOLO and break everything on the way out