Your party are going to murder the first NPC they come across, it happens, it's natural, they might be talking and they might not like his vague response, they may take a completely off the cuff comment you made and run with it and kill the NPC, and the whole town afterwards if you are particularly unlucky.

This is completely fine, you're all excited and getting into the spirit of things.

But other than that, discuss with the players their backstory and make it clear that they are a party and they trust each other if it's that sort of game, you might have a Gimli and an Legolas in your party and that's perfectly okay, but as soon as someone rolls a CN Rogue have that discussion there and then.

Prepare one or two random tables for loot, keep a Quantum Ogre handy if you're backed up against the wall and they go through you're whole content quicker than you realize.

You're PCs are either going to love or hate your NPCs, and be prepared to throw multiple hooks again and again at the players.

Keep a handy list of puzzles and riddles and maybe some generic monsters you can reskin as needed, goblins, wolves, orcs, human bandits and the like.

If you're going story heavy then I recommend DEFINITELY getting your characters backstory's, maybe even defining the party / adventuring guild before hand. Establish rules you would be happy to follow, not spilting up the party, any long term goals and dreams of the characters, players gender bending should also lay out how much they're willing to go in that respect (I gender bend my PC and she is having none of nobody).

But think and flesh out the people in towns, guilds and organisations, they will provide tons and tons of influence and really you won't stop getting ideas for quests and such.