Another reason is that the speaker is on the side with the home button. Having that edge face downwards when sitting down e.g. in bed muffles the sound. Not sure if this still applies to iPad 2, but it certainly does for the original.

I find that I'm often using the iPad "upside down". It wasn't on purpose, but there are very few reasons to care which way you're picking it up. It would be jarring to discover an app that cared.