Your Region will need a little attention before you start...
Let's begin by looking at your economy. Go to the Commerce Department and see what you are producing. Do you have surpluses or shortages in any commodities? Shortages in Electricity will probably hit you very hard, while shortages in agriculture, water and timber are often the easiest to make up for by trading. You make the most money by selling military, industrial, and consumer goods, so pay special attention to them. If you don't have enough of something, your minister can often buy the rest.
Choosing the right ministers can make a huge difference. Ministers come in three political flavors, with ratings in different skills. Every department has an appropriate skill, e.g., Military IQ for Operations or Defense. Liberal, Moderate, and Conservative ministers will implement policies differently from one another, so choose one that matches your style. Each ideology has members with excellent skills in the fields, so just browse through them until you find a minister with nearly full skill in the appropriate area. Be sure that you do not assign the same minister to two departments, however, as they will perform worse.
You will probably want to control unit production yourself. You can specify this in the Defense Department. The AI will build a variety of units (which you may not necessarily want) in each base, which can be difficult to manage. You will probably want to also control research yourself, which you can do by locking the <R> research panel.
Once you've set everything up, you can press <SHIFT-S> to save your Ministers, funding levels, and so on. You can then press <SHIFT-L> from a different game to load all of those settings.
If you ever don't know what to do, leave it to the minister, that's what he's there for.
Finally, start the game clock running! Learn from your mistakes. All my lost games can be resumed in 3 words. 'I forgot to...' 'I forgot to make a profit from selling goods.' 'I forgot to build supply units.' 'I forgot to defend my northern border'. If you need further assistance visit BattleGoat Studios' Forums.