When I asked for a good subway system, I got told it was not really possible in the current paks.
If you really want a subway game, you can try my pak http://forum.simutrans.com/index.php?topic=14891.msg146957#msg146957
where I guaranty that ever single passenger trains and trams from pak128 and pak128.britain are viable given the right circumstance. (quite a bold statement)
to answer the question.
Since it's a huge city, I'd first design 2 east-west road named H and Q which would roughly go at 1/3 and 2/3 of the city. I'd try to hit as much attraction and high density building as possible without making any hard turns. If I can go in the subway and i'm stuck in the roads, I'd also pay attention that those roads are as straight as possible. I'd favor trams to get a better speed bonus. High speed roads tend to be replaced by the city so it's not possible...
Next I make 2 north-south lines the same way named 8 and 17 to keep the pattern.
Once this is done, I'd start to draw my secondary line, let's start with G parrallel to H and right on the north of it. I try to draw it as straight as possible and to cover as much city area as i can, but of course, the straightest line is H... i do my best. Except that instead instead of making one big G line, I'd make 3 line separated by the line 8 and 17. I get G east, G west and G central. This way I sneakily encourage the passengers at taking one of my main lines for longer trip as their will be likely less transfer to do this way. But not to a point were they will start to travel sideway or something that would make me lose money in payfortotaldistance=2.
I repeat for all horizontal road identified with a letter and all vertical lines identified with a number until the whole city is covered by this pattern.