TLDR: Large changes to the game with the goal of allowing you to make interesting decisions ruling your empire in a game that will be much faster to play than Civ 5.
Game set up options:
Population, culture, and religion are tracked on a per tile basis and your people will automatically found cities when enough of them have gathered in a single tile. Cities production has been simplified to processes which convert production (citizen thought) into culture, faith, and research. More efficient productions choices are unlocked through the tech tree. Your culture will spread automatically bringing new lands under your control.
The tech tree has been overhauled and now conains 256 technologies, many of them new. In addition to the technologies you pick to research, your citizens will discover technologies automatically based on the focus of your civilization. If your people are farmers they'll discover technolgies like Irrigation and Fertilization, if they are traders they will discover Banking and Corporations. Trade units now spread your culture and religion to the land along their path making trade more important than ever.
There are fewer military units, but they improve automatically through technologies like Sword, Pike, Advanced Ballistics, and Laser Gun. Military units move automatically. There are no workers to manage since tile improvements are automatically built for you.
Civilization bonuses, religious beliefs, and social policies have all been updated as well.
Download is available here
Thanks to @Fish for a list of compatible mods.