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Force quit = option, command + escape key.
It would help if you told us which programs this was happening with most often. I use it most often if something on the internet is trying to force itself on me as if I were Windows and the browser gets slow and cranky. Force quitting won't hurt a thing - use it as you need to.
Sometimes I have to use it on Parallels/Boot Camp because that damn Windows Vista crap won't shut down, too.
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