Miss-able stuff, items in particular is often enough for me to loose interest in a game entirely. I don't care about miss-ables for the sake of completion, but if I don't have/am unable to get all the useful stuff at the end of the game because I was playing for fun and not following a walk-through it really ticks me off. If I am worried about missing stuff I can't come back and get then I tend to not have a whole lot of fun, and in many cases will just give up on the game entirely.