Like most reviewers have said: This is still Civ. If you played Civ5, then everything you know about the combat and diplomacy is the same.
The tech tree has been split into two trees now (Civic and Tech), with a LOT of new items filled in. The best part is that you'll want to CONSTANTLY look at the tech tree when making decisions, because they tell you exactly how to earn shortcuts on turns required for each.
The City unstacking is really simple on one level: Divide every building into categories, and allocate a hex for each category. ...BUT... Most Wonders take up an entire Hex. Some MUST be adjacent to the city center. Some must be adjacent to water. Most require certain terrain. ALL either provide or receive bonuses based on what's next to them. ...and you'll never, ever be able to build them all in every city (nor should you). It's not prohibitively difficult, but I'll just recommend that you specialize a bit until you get comfortable.
Workers build 3 things and then they're gone. (Can be upgraded.)
Caravans now build & upgrade all your roads for you automatically, so you'll find yourself picking routes based on where you want roads.
Culture is *WAY* different. I've won a culture victory already, but I kind of preferred the old "creeping death of culture" methodology. The archaeologists are incredibly cool, though... Digging through your own past wars is a fun concept.
Religion is both different and the same. There's a really bad "feature" where your religious conversion/spread units are based on where they were spawned, so it's a brutal learning curve. Tip: Don't ignore that Faith currency building up at the top-left, right near the gold counter you're always looking at! Spend, spend, spend, until you get close to Modern Era.
National Parks & Seaside Resorts are a stellar touch (i.e., where Religion meets Culture).
My only real complaint is the new "Amenities" system. It's a real drag/annoyance, and adds zero value to the game. The idea is that you're (rather heavily) punished if you don't build a lot of Entertainment districts for your civvies, which is costly. It takes the place of the Happiness system, but frankly it's just not fun. That said, a tip: Build entertainment districts in all of your cities, and put stuff in them.
Lastly, the game is simply gorgeous -- more so now than ever. I've never zoomed down to bird's eye more often in any Civ or Civ-like game than this one. The min & max zoom levels finally make sense, and neither impacts performance. Battles are so well animated & orchestrated -- special units included -- that it'll take you a LONG time to finally check that "fast combat" option this time. ...and the new "blank map parchment paper" fog of war is an elegant, gorgeous touch.