It's no secret Americans and the British have a bit of a disagreement on how to spell some of the words, not to mention pronunciation. Not to mention Canada, New Zealand, and Australia, either.
If your protagonist is American, while you are from a different side of the globe, how do you choose to spell your words? Do you change all of the text, only the dialogues, or stick to your "native" grammar and only incorporate the slang?
I'm from Los Angeles, California. And I have to say our "native" English is pretty botched. But I write the sort of English I grew up with, slang included sometimes. We've got the original Valley girls, who still talk like ohmygod Tiffany did you like see that? I stay away from that in my writing, unless I want to write a total teenager type character. Everyone here does say Dude too much, including myself, and I love to use that if my characters are friends or hanging out, or even talking to a stranger, Dude and man can have interesting effects in dialogue depending on who the character's talking to. Dunno, wanna, whatcha doin, yo, whatup, I use those too here and there because people use them when they talk.
We also have a huge Spanish cultural influence, which causes white guys to use words like amigo and homie. Most of the more recent English slang though, I can't stand.
Past that, the language influence comes from the books I read, some Palahniuk, some Spanbauer, some Bret Easton Ellis (LA hasn't changed all that much since his books), and some Clevenger. I haven't tried writing in a different dialect or different phonetics yet.
I use English spellings, as my stories are usually set in Britain or in an unnamed place, however if I'm writing a story specifically set in the US I use American English spellings (colour instead of colour, etc.).
I have no preference here, it's Same Same. But in all seriousness, I don't really care. As long as it's not like combining Japanese and Austrian. Even then that can be done well, if the writer is good enough and gives the reader enough frame of reference.
I had a story set in Australia with Aussie characters that was part of an Australian anthology, and I wrote it accordingly, used their spellings, their slang, made sure to use Metric measurements, etc. The editor also caught a couple things I'd overlooked, too. That was the only time I've done that. Usually I just use American everything, being that's where I'm from and where most of my stuff takes place. Otherwise I sometimes just do little things like choosing whether or not to capitalize God depending on a character's beliefs, etc. Which I've been told is wrong, regardless; it's just something I like to do. If I've got, say, a British character in my American story, I'll use their dialect and slang, but retain Americanized spellings.
Spelling-wise, I generally stick with American English, even though I secretly prefer the British style.
I generally avoid measurements if they require me to decide between metric and American systems. I'll just get creative and say stuff like "on the other side of town" or "as tall as a giant Christmas elf." You know, the standard stuff.
I have a bad habit of being long winded like that, if I can't find a single word to describe. I wouldn't even call my language American English at times. (I make up far to many words.)
It is more than just the spelling that is different. There are also differences in word meanings. The first that comes to mind is "pants".
I think writing to your intended audience concerning word usage is your best bet. Are you going to publish first in America or the UK?
My 2 cents.
Funny, the first that come to my mind are bloody and fanny.
I try to avoid having to write in unfamiliar voices. I've read and studied Victorian fiction so deeply that I might be able to pull off a Victorian Gothic voice, but I don't know if I will ever try it. It seems like it would be difficult to sustain an unfamiliar dialect for an entire novel without breaking character. It's possible, but I would have to do a lot of research and prepatory writing.
Actually the only reason it ever comes up, is if I'm researching a setting not drawn on a fantasy map.
Go with your intended audience, IMHO. If you're writing for New Zealanders, stick with New Zealand spelling even if its set in Iowa. If it's set in Rohan, or whatever you guys call that patch of grass with the hillfort on it, but you're selling it to Americans, spell it like an American; i.e. The Best Way To Spell A Word EVER!! (U-S-A! U-S-A!)