SimCity seems to me to be very well laid out. I had very few times when I couldn't figure out where something was. You'll spend the predominant part of your time in the city HUD noodling with your town. Occasionally, you'll head out to the region map if you need to get something from your neighbors or if you need to obtain another location to build an additional town.
City Planning HUDs
Heads-up displays (HUDs) are the network of icons that border your screen that allow you to do stuff in a game. I have collected here screenshots of all the various flavors of the main city HUD (like power, crime, etc) so you can see how the icons are laid out.
City Specialization HUDs
To customize your city, go to the city customization HUD -- located just below the primary city planning HUD on the left side of the HUD bar.
Menus
The menus may change before the launch of the game, so I'm going to wait until March 5th.
Settings
The settings will probably change before the launch of the game, so come back after the launch.