As this is a highly complicated game, we strongly advise you to take a couple of trial rounds in order to learn the basics before playing a full game. In our experience, the game can be finished in 2 hours. However, many starting players may take considerably longer.
The game is quite unforgiving: famine and pollution will pile up if your economy doesn't grow fast enough, which can lead to a slow and painful death.
In order to make the game more easy to master, we would suggest that you skip the Famine and Pollution phases in your first couple of games. This will make the game much easier (although still competitive) and allow players to acquaint themselves with the mechanics and intricacies of the different buildings and strategies.
If you rush straight into the full game, all of you may end up dead!
Always make sure to have a woodcutter (or another way to get wood). Do not ever, ever, EVER run out of wood! You need one wood to build either a woodcutter or a market (which will allow you to trade for whatever you need, assuming you have other goods).
If you do run out of wood and don't have a woodcutter or a market, the only way to get wood is for another player with a manned market to take pity on you and trade you one.
Build two or even three Cart Shops in the first turn.
Quickly get food production up to build 6-8 houses to ensure a decent workforce. Then, go for a second city.
Make sure you have sufficient food to avoid mass starvation. It's not the end of the world to get a grave or even a few graves. However, when you start placing graves you should also build a granary (if you haven't already done so) and/or start setting up more food producers. The famine level rises relentlessly, and you cannot afford to fill up your cities with graves.
Stores are essential for beginning players. Make sure you have sufficient storage. If your cathedral is dedicated to San Christofori or Santa Maria, you're fine. Otherwise, see if you'll have to burn goods because of insufficient storage. If you have enough room in your city, you may want to build a building even if you won't need it this turn.
Unless you have insufficient storage, don't feel like you have to spend your resources just because you have them. It is usually a good idea to keep your cart shops busy sending dudes out with wood to build producers out in the fields, but there's no advantage to building a city building until you need it. You may find that you need the resource or the building space for something else next turn.
Getting stone on your first turn allows you to build a cathedral on your second turn, which is especially handy if you're going to honor San Christofori or Santa Maria, since they'll let you store unlimited goods in your cathedral.
If you don't need an explorer and you're not going to have a cathedral with storage, you can use the wood to build storage. For one wood you can build a storage unit any size you want as long as it's a rectangle. In practice, we've found that a 6-square storage unit (i.e. 3 storage pieces) is usually sufficient.
You need to allocate resources for both the city and the fields phase during the city phase. If I put a man on a cart shop, I also put whatever resources he'll need on top of him so I don't accidentally use them to build something in the city.
When placing your first city, remember that you can place your workers anywhere within two hexes of your city, and they'll work that hex and all adjacent hexes that qualify (i.e. wood hexes for a woodcutter). Make sure to check out the rulebook and get a solid understanding of how the field hexes work; it's hugely important to grasp that before placing your city.
Try to make sure that you're within easy reach of a large patch of wood, at least one decent outcropping of stone, and as much water as possible. If you can reach an explorer or two, that's handy but not crucial. Meadow is nice, but since your patch of wood will soon become a patch of meadow, it's less critical than the other land types.
Water tends to be undervalued by newbie's, but it's important because it allows you to get not only food (fish) without a food seed but also two different kinds of luxuries. Unlike mountains, water can be re-purposed between uses, so the same pond can produce fish for one fisherman and pearls for the next.
Focus on winning as well as expansion! Most beginning players forget to focus on a winning condition and expand too much. Produce enough to win, but not too much.
Make sure that you're not running out of room in your city. It's a good idea to think about what you'd like to build in your city for the next couple of turns. If you won't have room to build what you need, you need to start stockpiling resources to build a second city.
Consider that if you build large countryside buildings, your investment will pay off longer, but your men will be away longer as well. Small buildings might be better if you are restricted by the availability of manpower.
Some Saints have "typical" combinations, e.g. San Giorgio and Stables, San Nicolo and Faculty of Philosophy, San Christofori and Faculty of Biology, a Given the price of buildings, you must choose wisely which other buildings to use!
Use Inns, the Dump, and Exploration to force graves unto other players.
Find creative ways to deal with pollution and graves-manage? avoid? absorb? export? Who would suffer?
Use clever techniques to block San Giorgio if he wins too often.
Adapt your strategy (and choice of Saint) to the starting terrain.