Full disclosure: I was a D6 x D6 Kickstarter backer, and have had more time with this system than the wider public.
D6 x D6 accomplishes what it sets out to do beautifully: it's a simple but strong system that can easily be adapted to any setting, with basic conflict resolution mechanics that feel designed to keep the story moving. The closest analogues are to something between Robin Laws' Drama System, in that occupations and skills are dependent on the individual game setting; and World, which keeps the focus on fast and fun narration. Players don't have as much agency as in World, and the rules are a little more dice-oriented, but the speed of play keeps the story rocking and rolling.
Character creation is simple: choose one primary attribute, choose an occupation, and choose Focused skills and Unfocused skills. Focused skills are skills the character knows, and unfocused skills are skills the character is in the process of learning. The more Focused skills you have, the higher your Focus number - which is the main number you compare die rolls against. The trick is, you generally want a lower Focus number, so becoming a "jack of all trades" with a lot of Focus skills means you're going to have a harder time accomplishing tasks than if you were super-specialized in one or two skills, but, you have the opportunity to use your Focus skills more often, so there's some risk-reward in character creation.
It also serves as a built-in safeguard against power gaming. :)
Gameplay is generally fast and fluid. The combat rules can seem a little bogged down with details - I suspect because they're designed to allow for the use of miniatures and maps, which introduces all the little wargamery nuances that systems like *World do away with in favor of keeping things moving along. However D6 X D6 strikes a good balance between mechanics and narration, and if you're like me, you can simply ignore the mechanics that don't work for your particular group.
I found the layout to be logical and the rules quickly explained in a way that makes sense. You're not going to do a lot of flipping around looking for things. The art isn't AAA-quality, but I've seen far worse on Kickstarters that made 10x the amount that D6 X D6 did. It does offer a nice, wide range of cross-genre images, clearly designed to inspire GMs (or Game Hosts, in D6's terminology) to experiment with different settings.
Lester Smith has created a solid, universal system that can withstand pretty much anything you throw at it. Recommended.