Forum ate my post, so a summary:
1) Rivers are going to be the main means of inter-civ trade, especially on larger maps. Roads take too long to get set up and are too vulnerable to barbs.
2) Speaking of barbs, get fogbusters out there pronto. There's so much land that barbs are going to be more of an issue than usual.
3) An early war is going to be harder on you; you'll rarely have true neighbors unless you set up extra civs for the size, so by the time your stack of axes gets to the other civ, their defenses are going to be much better developed.
4) The fact that it's spread out so much (and that there are so many hills for production) means that late-game military victories or space races are going to be your main modes of victory. If you're industrious, try a cultural victory; there's a lot more trees out there, so early wonders can be more easily built without sacrificing a whole lot of growth.
5) Value your flatlands. Production is abundant, but food is scarcer, and setting up cottages isn't as easy either.
5a) Likewise, Machinery becomes more important to get windmills set up to help feed cities in rougher terrain. Try a Chinese civ, since you'd be going for Machinery for CKNs anyway.
6) Don't start in the tundra if you can help it; if you do it's quite possible for your first three or four cities will also be locked in permafrost since the arctic band is so much thicker, and with a start like that it's hard to get set up for the late game.
This is all based off recent experiences on epic/noble/large with the standard number of civs. If anyone on Monarch or higher has any experience on Highlands, I'd like to know how the difficulty of early war affects the game.
