Don't be put off by the 'RTS' aspect. I'm very much a TBS player and I really like to consider each turn when playing games. Distant Worlds is not a click-fest at all and with the pausing you never feel rushed.
This game is so far ahead of the rest of the 4X genre games now. You can customise any and all aspects so that much of your empire can run on auto. Personally, I just set the game up so that fleets are controlled by me but individual ships are controlled by the AI. The AI will then look after empire defence while the fleets do the main work. I tend to over-ride some research - but not much. And I let the AI handle most of the espionage and diplomacy. I'll design a few ships when I need something specific but generally the AI will also do a good job of this as well.
The 20-odd unique races also play differently and each game is always interesting as you meet each neighbour. Some races like each other and others don't. Some are aggressive, some are back-stabbers.
The biggest suggestion if you get it is don't feel constrained to play as the Humans (I think most people start here). Depending on what race you play will have a big bearing on what strategy you need to use when playing the game.
This is by far the best game I've played in 2010.
--- EDIT ----
I should also point out that the game doesn't really play like one massive game but rather a series of smaller objectives.
For example, in my current game I've taken an important planet in a distant sector and it is a long way from my main planets (and so is a distance away from supplies). I have no fuel in this system so I have needed to build a special resupply ship to deploy in a neighbouring system. To do this I need to have a fleet of ships that can protect the resupply ship. These need to be designed specially with extra fuel-tanks so they can fight at a distance once they are there. Once this fleet is refuelled I can pack-up and send them all back to the important planet to protect it while it builds its own starbase and defences. Once these are in place I can use the fleet to start taking other systems in the sector. And so on and so on.