We run sites in Australia, Canada, UK and the US, and the issue of spelling is extremely important, if you do not want to upset some of your visitors.
A couple of years ago, we did not REALISE the importance of using the word "Inquiry" and not "Enquiry" on our contact form page on a US targeted site. We had this pointed out by several visitors, and so made the changes.
I am English and was moved to the US in the early 80's by my parents, where I was enrolled in high school. One of my favorite stories was asking my 30 something, female math teacher if she had a "rubber" I could use. Luckily she understood the different meaning of the word, but the rest of the class, it was the funniest thing they had ever heard.