I would strongly recommend Distant Worlds with expansions as they improve the game out of sight. It is available here: Link
The only problem is the ridiculous cost of it and that it isn't available on Steam (if that's important to you).
The game itself plays in real-time however is easily paused to make decisions, give orders or make changes. The game difficult ranges from people just starting to learn the game (they can keep most of the games' systems automated) to those that play on the hardest difficulty and also manage every part of their empire manually without any AI involvement.
I recommend this game to anyone that loves a good 4x strategy game. However, I would probably wait until the price comes down before shelling out around $60-80 for the base-game and expansions.
There is a new expansion planned for release this year as well and whether or not it is released on-time, I'm sure Matrix Games will likely put the game on sale around December or Christmas/New Years.