Use the 960 grid as DCD says above.
Easy to work with from mock-ups in photoshop/fireworks to including in your html. You'll get a layout quickly once you familiar with the simple concepts of the grid "framework". It takes care of the margin/padding stuff for you.
Many top site designs use this grid.
As for you questions specifically:
960px width (using 960 grid):
container_12 and inside of that include a 9:3 or 10:2 grid layout for 2 columns
OR
container_16 inside of that include 3:9:4 grid layout for 3 columns
But there are no hard rules on this. Make it work depending on your context & use.
If you provide more info on what you intend doing, I could give you more specific advise :)