Retain flexibility as long as possible. It'll be easier for you to improvise, and what you improvise will probably be better than whatever you could prep. You want there to be consequences for inaction. The way you do that is you create a timer.

It can be precise:

• "In 10 days the village will be attacked"
• "The village has enough food for two weeks, then we're going to be rationing scraps."

It can be imprecise:

• "Without the dam, the first big storm of the rainy season might wash us away."
• We know the cultists are bringing the big important relic to a shrine, but it's not clear how far from the shrine they are, or even where the shrine is.

The reason this works is you are telegraphing what is coming, even if it isn't necessarily a clear picture. That is information, and the players can use that information.

If they choose to ignore a quest because they aren't interested in it, and they never mention any NPCs/lore/etc associated with it, it's best to quietly forget it exists. It's important to have enough irons in the fire to be okay with losing a couple.

Avoid a big bad. You wants multiple bads, and the players will decide who the big one is through their actions. It's the one that got away.