There is a lot to miss in Witcher III and a lot of it has sort of kind of a major impact on the ending and some of it just quest rewards and flavor lore within the world. The thing that you can miss the most is secondary quests, but there are some oddities that can happen. To avoid anything, I've put together the best guide I can on some general things that you can miss without spoiling much of the game.
Some secondary quests are missable, generally they fail if you move on to the next chapter, but some do not. For instance, every prologue secondary quest can be failed. Should you not act, in the time you go to the second chapter then they will fail and you will get a lot of cool instant endings. For instance, if you give the girl the potion then she may live or may not, if you don't then her fate was sealed. Who you sided with when it came to the dwarf's forge will determine if he's rebuilt or hasn't.
This continues further in the game. Assume that at the end of a chapter, any quest you haven't done is gone. Now, just to make it clear, chapter I is long, very long, so there is a ton of time to do everything. Chapter II and III have much fewer secondary quests. To note, many secondary quests will still be completable after the main quest is done, but I'd suggest doing as many as you want now.
Secondary quests are rife with other missables. For instance, the secondary quests must be completed to get the "good" endings or even a choice in it for: Bloody Baron, Keira Metz, Sara, Whoreson Junior.
Additionally, the difficulty of the final mission is determined by how many allies you make. Don't worry about this for a bit, they don't start showing up until you explore a bit. However, the more allies the easier the later part of the game maybe.
If you like a character and want to control its ending, do every quest they offer you and never ever forget to return to them later if they say so. Sometimes you have to finish some main quests and other secondary quests for a quest to unlock.
At the conclusion of Ugly Baby, when you are told to gather help, this is when the majority of secondary quests will be abandoned if you do not do them. You have between Prologue and Act I's start to do the Prologue quests and between Act II and Act III to do all of the secondary quests in the world. Anything remotely related to recruiting heroes will fail when you move to the Isle of Mists, including many of the quests that affect the ending.
Towns - Merchants, Quests, Etc.
Towns will populate and depopulate based on your actions. If you reach a point where you failed to do something, a town may or may not exist along with its services. Additionally, secondary quests may or may not be available.
If you turn down a quest, unless it's the main story, there is a chance you're done. For instance, in the main quest you can refuse to help a man with his goat. He'll wait forever for you to return and agree. Yet, many NPCs will ask for your help and if you say no, be done with you.
Witcher III is one of the first games I've personally played where decisions really matter. At various points you'll have to make some choices, these will drastically alter the course of the game and how you complete quests and can turn some quests into a long drawn out painstaking task or a simple dialog option.
Some brief spoilers, but to give you an example, at the start of act 1 you're prompted to either fight or drink with some folks who aren't very nice. Shortly, you'll run into them again. This time guarding a door. If you were kind and nice, they let you through. Mean and short or deadly and you'll have to come up with an alternate way past that door.
Once a choice is made, unless it's a main quest, you can't come back to it without reloading. Save often, because a simple choice can have a long term impact on the game and/or result in the death of main characters.
Things That Don't Go Away
Contracts, for the most part, are forever. You can pick them up and start them at any time. Additionally, treasures, places of power, main quests, and loot throughout the world will never change. Secondary quests that involve travel (i.e. things blocking the road) will usually never change as well, perhaps you could easily say, most secondary quests that don't actually show as a quest will never go away.
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