Hub in a smaller airport (say, ~25M pax) so that there'll be a decent pax base but less competition.
After what I've seen in world 9, I've learned a few lessons:
1. Grab a gate at the big airports early on... or don't plan on flying there. Ever.
2. I like to start off with the cheapest aircraft in the game that will work for my needs and order as many as I can, whenever I can just to get routes out... I don't know if it's a good strategy but it worked for me in World 9. (although I started 2 years into the game)
3. Join an alliance with global coverage preferrably, but definitely with bases on your home continent.
4. Use brokers when you can -- if you stay loyal to a specific broker you might get better rates.
I'll be serving the eastern United States for around half a year before moving west.