What kind of game are you trying to play? That makes a big difference. For a duel, I like a mirror map. For a team human vs. AI, Highlands or Tectonics tend to produce interesting maps. For a big free for all game, lakes, pangea, or Tectonics are good. For a larger game, it's a good idea to have someone preview the map and edit start locations to make things fair.
As far as settings: I hate lairs because they're so imbalanced (Yay! I won/lost the game on turn 3!). Placing lair guardians is an option if someone is making a map for you; otherwise, I'd strongly recommend turning lairs off. I really, really, hate tech trading - it makes it mandatory to group up in a tech block or you'll be left in the dust. Acheron and Orthus are both really poorly balanced. Some people argue that Living World is more fair than leaving it off, since the quality of events will tend to even out as the quantity rises. I'm skeptical.
A lot of the settings also depend on the style of game you're trying to play. Large maps will let the players play builder in their own corners, and result in wars with much more advanced units than small maps. If you like diplomatic contact, a small map will bring that into play a lot earlier. Simultaneous turns and sequential turns are really completely different games; in the former, reaction speed is probably as important as strategy (double moves with super fast units can be insanely powerful; don't even mention Blinding Light). You can start with simultaneous turns and convert to sequential when war starts for the best of both worlds: faster early game and TBS instead of RTS warfare.