Besides D&D, I also like GURPS. The advantage to GURPS is that you can
legally play just about any type of character that you want. Want a mage who can fight with a sword? No problem. Want a gunslinger with a hidden supernatural gift? GURPS will allow it! Want a werewolf biker? Yes, you can with GURPS. Want a semi-neurotic teenage anime mech pilot haunted by the demons of his past? You get the point...
The main problem with GURPS is that it tends to be very "realistic". You can only take your health score worth of damage before going down. Since your health score never really increases (unless you spent a high amount of points on it) characters never really get tougher to kill. I've seen high point value characters get taken out by thugs with guns. Hence GURPS works best with modern war and cyberpunk type games. GURPS can play high fantasy, but it doesn't really capture the feel as well as D&D does.
One other potential problem with GURPS is that it is so generic. The core book gives the basic rules needed, but you really need to get several other books (specifically Compendiums I and II) if you want to go anywhere with it. You also kind of need a good gamemaster to create a good campaign out of the overly generic rules.
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My other favorite system is a little known rpg called Imagine (
http://www.role-playing.com) In some ways Imagine harkens back to 1e D&D with the simple illustrations, lack of flavor text and pregenerated setting, and occasionally dense rules. However, it is one of my favorite rpgs. I would be playing it instead of D&D if it had the fan base! One of the things I like about Imagine is the variety. There are dozens of classes and races to choose from. DMs can pick and choose which classes and races to allow in the campaign. Since classes are essentially a collection of skills that are acquired on various levels, creating new classes or modifying existing ones is fairly easy.
The one drawback (although in my opinion it's kind of an advantage) is the detailed combat system. Combat is divided into 10 second rounds. Each action takes a certain number of seconds. Players can do as many actions as they have time for each round. There are numerous hit locations, each with a different effect. Players can't just say "I attack", they must describe where they are aiming at, and the method of attack (striking straight on, cutting crosswise, etc.). The combat system is basically designed for the detail freak.