Indeed, you can miss out on some pretty major quests. One notable quest, "Duchess in Distress", contains cinematics and pivotal character moments, but it's only available during the brief period of time between the Duke assigning you the Greatwall expedition and going to the Tainted Mountain. These two quests are directly side-by-side, and the Duke makes the expedition quest to be of top priority, but the only way to get "The Duchess in Distress" is to ignore his directive and fart around for hours before going on this very important mission.
The most maddening part is that the quest is still available after you complete the Expedition, but it cancels itself the moment you accept it because you missed the "deadline". If I can't do the quest, why is it still being offered? I hesitate to call DD's quest system broken, as you can complete every quest if you know exactly when they're available, but it's undeniably obtuse and unfriendly.
I could understand a system that shuts out access to certain quests based on decisions you've made, but realistically the only way to complete every quest in the game is to explore every single backwater containing NPCs, not once, but after every quest you complete and every level-up. With no system of convenient fast travel, it doesn't quite work out. You really need to know exactly when these quests are happening to save a lot of wasted time. I think it needs work in the sequel.