Oh my. That is quite the question. My first thoughts go out to Trixie or Pinkie. I'm good with people who have a superiority complex, like Trixie, so I think that I could be a good friend with her. I'd also love being friends with pinkie, simply because she could make me smile, no matter how depressing my day has been.
However, the problem with being friends with one of those two ponies is that I'd develop a crush on them, and that could potentially destroy the friendship. I have a terrible habit of developing strong emotional attachments to friends of mine who are female, and 99.9999% of the time, they don't feel the same way, and that's devastating.
So, In conclusion, I'd be best friends with Big Mac. I wouldn't develop a crush on him, he's a pretty cool stallion, he's hard working, and he's just a pretty chill guy.