"Wait on" vs "wait for"

It's regional in U.S. English. Much of the U.S. says "waiting for you", but I believe that much of the South says "waiting on you". I don't know exactly what regions use "wait on" (not the Northeast), and a couple of minutes of Googling didn't find any answers, so I can't be more specific.

Wait on has numerous meanings. In the OP’s example, it means, in the words of the OED’s definition, ‘remain in one place in expectation of’, in other words, wait for. The OED’s citations supporting this sense range from 1694 to 1984. The OED gives no indication of regional bias, but I wouldn’t say the use was ‘widely spread’. As for ambiguity, most of the time context removes it, and I would say it would generally do so in this case.

"Wait on" as a synonym for "wait for" is something I've heard much more in US English than British English, but it is used in that sense. They're pretty much synonymous. And yes, you're right that the sentence "your sister is waiting on you" is ambiguous, and so it's probably best to avoid using the colloquial "wait on" for this meaning.

I think to a considerable extent the choice of preposition is regional, stylistic, or simply arbitrary, as other answers indicate. But in the UK at least, whereas I'm waiting for John is much more common than ...on John, there's a difference in how we add more detail...

I'm waiting on John [doing something]

I'm waiting for John [to do something]

...so it's always I'm waiting on John arriving or I'm waiting for John to arrive, never the reverse.

If it's obvious what we're actually waiting for John to do, we often omit it - particularly if we're just waiting for him to arrive. But as mentioned elsewhere, even Brits are likely to use on, not for in respect of computer code waiting on a status flag (changing in value, which we invariably omit).