The Murderhobo's Hierarchy of Needs
Maslow's Hierarchy of Needs is - as you may learn from the linked Wikipedia article - a flawed concept. It may model the way some people operate, but people and their circumstances are unique.
You may remember old Maslow from your high school sociology classes. He organizes the various needs people experience into a hierarchy and suggests that lower-order needs must be satisfied before higher-order needs are are considered. If you don't have enough food, you aren't going to bother with building your reputation, for instance. We know this isn't strictly true. People prioritize all kinds of things at the expense of other, more foundational needs.
No bother. It may be a broad and often inaccurate generalization, but it's still useful for DMs as a guideline for finding the juiciest spots to stick a dagger in your player characters.
At low levels it isn't hard to threaten a D&D character. They have limited hit points. Their resources are scarce. Throw a couple of goblins at them and you don't have to try hard to knock at least one of your players down.
If you are like me, you may sometimes struggle to threaten your players as they become more powerful. It can become increasingly difficult to invent plausible mechanical challenges for them. All the online tools to generate CR-appropriate encounters for high level characters suggest things like "two hellhounds, four giant alligators, two djiinn, and a draft horse" which... well, I don't want to speak for everybody, but that isn't exactly a natural fit for my particular game setting.
Actually, if you can make a coherent encounter out of that, please share it with me. I'd love to see it.
Also, threatening your player characters' HP pool at high levels of D&D just doesn't mean much. Even if you can get through their endless defenses and kill them, they can usually resurrect with minimal inconvenience. So, how to threaten player characters?
Enter: Maslow's Hierarchy of Needs.
In case you are reading this on RSS or the image didn't load or something, here's the list of priorities in order from most foundational to most aspirational:
Physiological: This is stuff like food and water. Air to breathe. The stuff that keeps the human body operational.
Safety: Avoiding dangers. Financial security. Managing your immediate health concerns.
Love and Social: Making and keeping friends. Family, biological or found.
Esteem: Gaining the respect of others. This could be fame, or it could be smaller scale.
Self-Actualization: Curiosity, skill building, philosophical reflection. That kind of thing.
So we don't try to threaten the player characters directly. Threaten those things instead.
Your game may differ, but generally speaking it feels like the Hierarchy roughly matches the progression of a campaign. The players start with very little, often struggling to find shelter, maintain their supply of food, etc. They are struggling to meet their Physiological needs. As they progress they gain resources and familiarity with their surroundings, so they have that Physiological stuff on lock. They then start looking to higher-order needs. Establishing a home base. Learning about the dangers of the wild. Finding work. This is all in pursuit of their Safety needs. Then they move on to finding allies: Love and Social. They move on to Esteem concerns, which might be them becoming heroes of the realm. Finally, they decide how their characters will retire, or what kind of demigod bullshit they will pursue, which is Self Actualization.
Your players may do something different, but this is roughly the arc a standard D&D campaign often takes.
So, how is this useful? Easy. Figure out where they are in the Hierarchy and threaten the things around that area. If they are still scrabbling around in the dirt trying to find a reliable source of food you can directly threaten their hit points to great effect. But if they have progressed up that Hierarchy at all you have the ability to threaten them in effective and indirect ways.
Physiological: You threaten their source of food, water, or shelter. A predator moves into the fruit grove. Gnolls have despoiled the well. A blight hits the local bird population. A tornado messes up their lean-to at an inopportune time.
Safety: Threaten their connections to commerce and make their surroundings difficult to navigate. The duchess says coins with the old king's face are no good anymore and her guards patrol the market. A dragon is patrolling the region and makes travel dangerous. The pox is going around again.
Love and Social: Their friends are in danger, or they have reason to dislike them. They take the opposite side in a civil conflict. They are being forced to move far away unless they raise enough money to pay their debts. A suitor comes to town to woo a player character's sweetheart.
Esteem: Spread nasty rumours. Someone frames them for a crime they did not commit. A fact comes out that undermines their accomplishments. Their long term goals are called into question, framing them as a potential threat to the realm.
Self-Actualization: This one is a bit tricky to threaten, honestly. Maybe you can try to make characters doubt their own worthiness, or make them question their own long term goals. Is the world worth saving? Are people doomed to make the same mistakes again and again no matter how hard you try?
Wherever your players fall on the Hierarchy, the juiciest targets are most likely the layer they are on and those immediately around them. You can threaten the thing they just got, the foundation upon which their recent acquisitions are built, and the stuff they hope to acquire next. If they are desperate for a meal, threatening their reputation is likely not effective. Likewise, if they are big damn heroes, threatening a water source is useless: they have friends in high places who can easily replace what they'd lose. But if they just solved their Safety needs, you can still threaten their Physiological needs, or put up obstacles between them and solving their Social needs. With all things, your circumstances may vary.
It's worth noting that this should not be an arbitrary punishment. Don't just smash your players' new toys. Tie them to the tracks and then point to the locomotive coming around the bend. A blight has been reported in the north and it's spreading quickly south. Bandits have kidnapped your favourite little weirdo, but they are probably still alive! What are you gonna do to fix this??
Hopefully this is a useful lens through which you can examine your campaign and find places to make your players sweat.