Here's my 0.02 Basic Units of Currency, in no particular order:
True20: A streamlined d20 variant that shares many mechanics with Mutants & Masterminds. Characters can be customized easily and with fewer rules than in D&D. The only part of the rules that might take a while to get used to is damage, which is not quite as clear & simple as I'd like. (I've had a couple articles published for the system, but haven't had much chance to actually play it.)
Earthdawn: I love the system and world (and I finally get to play again, now that my wife is starting up a game!), but the learning curve can be a little steep at first due to the unusual dice mechanics. It has some of the same feel as D&D, with races & classes & levels, but how you use those XP to advance is handled very differently, and it has its own distinct flavor of magic.
Call of Cthulhu: Chaosium's Basic Roleplaying system is fairly simple, using %-based skill rolls for everything. CoC (the only version I've tried) is easy to customize skills-wise, but there's not many other character options (unless you acquire some spells and/or insanity). Pagan Publishing's
Delta Green setting is the best treatment I've seen of the modern-day Cthulhu Mythos, casting the PCs as law enforcement types who have legitimate reasons for getting involved and carrying all those guns.
Cinematic Unisystem: Largely point-based character creation and simple mechanics make
Buffy,
Angel, and
Army of Darkness fun and easy to play (and fully compatible with each other), whether you're using the canonical setting or not. These games acknowledge the power disparity between Slayers and Scoobies, but the Drama Point system helps alleviate that somewhat. (An all-Hero game is a viable alternative as well.)
GURPS: I've run 3E and own 4E. In both editions, the basic mechanics of are fairly simple, and allow play in any genre(s). Character creation is extremely flexible, enough so that new players can get lost in the sheer volume of choices. I'd highly recommend trying
GURPS Lite first--it has the basic mechanics and a solid selection of character options, and you can add more complexity later with the fully-compatible Basic Set and various supplements.
BESM: I've run both 2E and 3E, and prefer the latter (better point balance and more defined customization). It's one of the more rules-light games out there, without sacrificing the ability to fine-tune characters, and it handles a variety of genres well, which is why it's my system of choice at the moment. (GURPS used to be, once upon a time, but BESM does many of the same things more simply.)
...But whatever you do, don't pick
Hero System! Our group is new to it except for the GM of our upcoming supers game, but the arcane mechanics and math are giving us all headaches--and that's just char-gen.
