I've always enjoyed GURPS for fantasy. I like the point based character creation, gritty combat and DIY approach to creature creation. I love tinkering with monster and NPC builds.
GURPS probably makes for a good study in contrasts with D&D since the two have so vastly different design goals. D&D (especially 4E) strives to emulate one particular style of play, with a lot of setting assumptions, and do it as well as possible.
GURPS, on the other hand, says:
"OK, we start out with a blank slate - a world following real life physics, with people having the capabilities of real-life people. Then we start throwing additional stuff in."
GURPS starts with a fairly close approximation of real life, distilled for gaming purposes so that it isn't overly complicated (well, that can be argued - but if you start with GURPS Lite, which is
freely downloadable, you get the basic rules, including character creation, in only 32 pages - a good starting point). Tactics and strategies which work in real life are rewarded. In medieval settings, wearing armor is a life saver, and surrounding your foe is very effective. In modern-day settings, moving quickly and using cover are vital for surviving a firefight. And so on.
Then you start throwing
other elements in. Whether magic or ultra-tech, whatever you choose to add to the setting will be able to interact with "mundane" technology and abilities, and you will be able to work out its implications in fights with few problems. And the range of possible additions is vast. If you can
think of a specific source and feel of a certain set of supernatural powers, you can probably stat it up without too many problems. Necromantic powers which allows you to create numerous undead servants? No problem. Summoning elemental effects which leaves you fatigued? Easy. Using the power of nature to shapeshift in animal and plant forms - or just part of your body? Hardly any work to stat. Psionic powers of telepathy or telekinesis? All there in the book. And so forth...
What may be difficult for beginning GURPS GMs to adjudicate is the concept of "game balance". It's inherent in D&D 4E, but GURPS character creation is a
lot more freeform. It's exceedingly simple to create one character who is a total combat monster, and another who is useless in a fight but utterly charming in any social environment. Talk about these issues with your players, and make sure that everyone has their time in the spotlight.
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