Most NPCs related to major quests are set as essential, so they can't die. I wouldn't worry about it too much.
The only really major thing you should know: If an old mage in the North sends you to fill a cube, and you have to use a machine to do that,
Spoiler don't grab the item you might find in the machine, unless you have the quest for that too.
That'll break the Main Quest.
I've seen one quest broken by waiting too long so far in about 350 hours of play with 3 different characters. A dog needed for a quest disappeared after I'd avoided him intentionally for 80 hours or so.
Can anyone guess why he was avoiding said dog? I don't know what dog he is referring to.
Also, which quest is this, and how can I do it early so that he never disappears?
Last, why do I keep hearing about it being important to do the blood on the ice quest as early as possible?
I thought it would be fine if you just avoided it. I was planning to do it later, and make sure to make a save just before triggering it, in case it bugs.
I dont know anything about the quest, though.
Help, anyone??