This happened to me last night.
I'm kind of new in this kind of games. Just started playing this, Tales, and Strong Bad Ep1. Got lured into the genre by a friend of mine, and am actually liking it.
So, I'm in Monkey Island. Just got the key to the Monkey Head, and got in. Didn't mind going back to get a map, or anything. Just jumped inside as soon as I got the key. I got told afterwards that I needed to go with the cannibals before entering the head.
Anyway, I'm just walking around, learning that the rooms are randomly chosen everytime you enter a cave or walkway, but trying to find a way trough. Remember this is the first time I ever played this game. I saw the noses, hands, eyeballs, little heads, even a monkey brain. Walked around for some time.
In one of the rooms I entered, I got in the room from the left side of the screen. I don't remember if it scrolled from another screen or if I came in trough a cave. The thing is that upon first entering the room , there's some pillars that I can't get trough. They look like big spikes coming out of the floor. I can see to the right of the pillars some small heads in the floor, and when I look at them he says he can't reach them. I also see a cave entrance further right. But I can't go there because of the pillars. So I decide to go back.
To my surprise, I can't. Turns out Guybrush is stuck at the farthest left in the room, so when I click on the border of the screen he just moves up or down, because the cursor is above or below him. He doesn't move to the left. I can't move to the right so the click on the border registers as a movement to the left, because of the pillars blocking my path. And to my bad fortune, autosave kicked in while I was there, so there's no re-loading.
I know I should have saved more (my only save file is from when I was doing the Three Trials), so it's a little my fault for counting on the autosave, but I really think this is a game-ending glitch that will make have to re-start the game, and should be taken care of.
Anyway, sorry for the long post. Just wanted to expose my case, as it gave me a lot of frustration last night.