[Natsu]

If someone says "excuse me" in an angry voice, it's sarcastic. If someone says "excuse me" in a soft voice, it's genuine.

Or something like that, anyhow. It's certainly possible to make it ambiguous, in which case it will simply be interpreted according to the mood of whoever hears it.

[albemuth]

There's also the loud "excuse me" with upwards inflection which denotes the person has taken huge offence.