The differences are mostly in the 'locale' issues, especially dates. I got around that by doing 'Jan 1st 2009', in stead of the strictly numerical options.
The language issues are less of a problem, they're minor spelling issues such as 'colour' vs 'color'. I never had any complaints about those.
Australians and Canadians have long ago dropped most of their English spelling details, Americans don't care too much from what I can see. Some very purist English folks have sent an email or two (one about 'gray' vs 'grey', go figure...) but for the most part it is just whatever works.
There is a lot of tolerance for this in end users, they understand that you have to make choices.
Here was an interesting thread on this not that long ago: