The first thing you should do is go to Setup -- it's the "gears" icon on the top-middle of the interface.
I recommend going thru the Profile Settings first, where you can set a number of options in the system. There's 2 pages of options, and I suggest going through them all to familiarise yourself with all of the options in the system. Take your time, there's a lot of options here and it will give you a good idea about all of the features, too.
Once you save the Profile Settings, save it, then you have to log out and back in for the settings to take effect.
If you want to over-ride the Profile Settings, each user can change their Personal User Settings (User Preferences option) so that they can have a more customized system.
Go to Setup again, and make sure that you have all of your company information correct in Update Organization.
I always suggest that you turn off any features that you won't be using. Go to Setup Tabs and Setup Left Menu to disable all of the features that you don't need. This is really important and helps lessen the confusion -- we have a lot of buttons.
Security Settings are where you can set how administrators & regular users access the CRM system. There are a lot of options that let you control access and secure the CRM. In the Manage Users area, you can add your co-workers, change their passwords, inactivate a user and make a user a regular user or an administrator.
In the Data Setup area you can create custom fields using Setup Extended Fields which are fields that you need that are not default in our system. You can add as many as you need. In the Setup Field Sets area again under Data Setup you can customize all of the workflow fields and default values in the system, such as Priority, Status, Deal Stages and more.
Spend some time in Setup getting to know all of the additional features here, most are self explanatory but it won't take you very long to become an expert. Our system is powerful, but it's simple, too and spending about 1-2 hours in the Setup area is highly recommended.