When people use the word "Retard" in any context.
It's just a horrible word, a lingering relic from when society was even more of an asshole than it is now. Using it to describe someone with Autism, or Down's Syndrome, or any other mental disability, is just plain cruel in my eyes. Technically true, but then again, so is calling an African-american a...well, you know, and that's a horrible thing to say either.
However, what REALLY grinds my gears is when it is used as an insult to someone who did something stupid. We already have words like "Dumbass," "moron," and "idiot" for that! Unless you mean that they actually are mentally disabled, then not only are you insulting the person you direct it at (for insinuating they are mentally disabled, which many people do not like), but you're also insulting people with mental disabilities (for insinuating that people with disabilities are all complete and total morons).
It's just sickening.