If you’re a football newbie, I’d say go with Madden 2003 instead of NFL 2k3, because Madden has a training mode as well as mini-camp, both of which are designed to improve your game and teach you some things about football.
Training mode is great for teaching you the fundamentals of football offense, in that Madden explains the reasoning behind certain formations and plays, shows how they’re executed, and lets you try it afterward.
As far as defense, the formations delineate the ratio of linemen to linebackers to defensive backs. A 3-4 and 4-3 defense use 3 linemen and 4 linebackers, or 4 lineman and 3 linebackers, respectively. In general, lineman are strong and right up at the line of scrimmage, and therefore are good for rushing the quarterback or stopping runs. Linebackers tend to be more versatile, in that they can move up to stop a run, fall back to guard against passes, or look for openings to rush the quarterback. Therefore, linebackers should be more agile than linemen, but might not be as strong. Defensive backs (cornerbacks and the strong and free safety) are used to defend against passes and occasionally sneak up to rush the quarterback.
Remember, though, that the preferred defensive formations of a team should reflect their strongest player positions - if your team has more great defensive ends and tackles than linebackers, use a 4-3 to take advantage of that. If you have lots of good linebackers but weaker defensive linemen, use a 3-4 mostly.
The Nickel formation adds a 5th defensive back to the field, instead of the usual 4 (2 cornerbacks, 1 strong safety, 1 free safety), and emphasizes pass protection more than the 3-4 and 4-3. Likewise, the Dime formation stresses pass defense even more than the Nickel. Consequently, these formations make themselves more vulnerable to a good running attack, but add much better defense against a passing game.
I’m still not sure what the 46 defensive formation is, though.