I've acted as DM/ST for a few RPGs in my time. Not quite twenty years yet, but still, it's deep in the second decade right now. During that time I've come across some little sayings that - while only sometimes true - can make one's life in charge of an entire world that much easier.
1) Never throw a stick you don't want chased.
It might seem like a trivial throw-away detail to you - something that isn't worth worrying about, a minor piece of flavour to lend a hint of exoticism to your world. Be careful, though, because players pick up on details. They think - they overthink - they form conjecture. They'll chase that stick you just threw, whether it was an important stick or not. That movement in that shadow? They will want to take a look at it. The cursive handwriting of this note? They'll want to look into that. Be sure you know where a party will end up going if they chase that stick before you ever throw it - or at least be confident that you can think on your feet fast enough to keep the game going.
2) Never assume the stick will be chased.
On the flip-side of the previous point - don't be surprised if sometimes that juicy plot hook is actually passed up as apparently being a trivial throw-away detail. Sometimes it won't even be that players miss the potential story - sometimes they just don't want to go down that route. That's fine. Gaming is an exercise in character and journey, after all. Make sure there's alternatives or that you're prepared for a divergence - multiple sticks can sometimes be useful.
3) Detail and saturation are not the same thing.
It's very tempting to flood a setting with detail to try and give it that extra bit of depth. Don't. You only need so much - a hint here and there and people's imaginations will do the rest. Work the detail of the setting into the interactions the characters have with it, and you need never drown your players in exposition. It's like tricking people into learning - make it fun and it stops being a chore.
4) Be prepared, think fast.
The twofold strategy at handling anything your players do is thus: plan until just before you think you have enough, then freestyle the rest of the way. As long as your setting has a foundation, and you have good NPCs you can fall back on, then making it up as one goes along is no great crime. It can be pretty fun, too. That said, if you are thrown a huge curve ball, never be afraid to take ten minutes to rethink your plan or work some notes for a new approach.
5) Always have a surprise up your sleeve.
Things moving too slowly? Players plodding through a town they don't necessarily need to be in? Surprise them. Do something they aren't expecting. Stir up the status quo. Throw in a non-plot-related encounter with something they couldn't predict. As an added twist - work it into your plot in a way that isn't obvious yet. The life of an adventurer is filled with surprises.
6) They aren't your Sims.
It isn't you versus them. You have literally the entire world at your command, and they are a group of individuals within it. If the story is going to be about persecution and grossly unfair odds, tell the players beforehand - because most players come to the table expecting fairness and fun. They're people, not digital representations of people.
7) Don't be a dick.
This should be obvious. Randomly being an asshole to your players, constant bad jokes, mockery for no good reason - these things aren't acceptable in real life, they shouldn't be acceptable at your table. Banter and witticism between friends is okay. Abusing your position as DM to get away with being a dick is not. Learn that line - we have to do it in real life, after all.
There may be more to this later...but for now this will have to do.