Anno 1404/Dawn of Discovery
I got this game the other day and HOLY SHIT. It's so great I felt compelled to make a post about it. It's what I've always gotten a hint of when playing various genres like the RTS (Age of Empires series), TBS (Civilization Series), city builders(Sim City), etc. There was a certain style and gameplay focus I was looking for that nothing else, save Civ IV: Colonization (only to a certain degree) ever touched.
http://anno1404.wikia.com/ (game info)
There's a huge focus on exploration, trade routes, diplomacy/reputation, city building, managing your population's needs/desires, resource/production logistics (farm the wheat to mill it into flour to bake it into bread, to feed your population so they advance in social class to ultimately provide you with more taxes) What I love about it especially is that combat isn't really forced upon you. You don't feel the need to build up a huge defense for fear of being rushed. Pirates might try something, but you can pay them a reasonable amount to leave you alone. That being said, I do choose to engage in combat at certain times, like buying a "privateer pass" to raid an ally's ship that just left their base with a hull full of goods. There's also quite a few quests that the neutral NPCs give you, like to sink a particular ship, escort a trade ship, rescue castaways, and even a "where's waldo" type of quest to find a particular wanted person in your city. Lots of different things to do!
The only real downsides is that some of the concepts take some digging on the wiki page to quite understand as the tutorial and manual do a poor job of explaining things. Also, while the game starts off fairly manageable it can get incredibly complex later on when you have multiple colonies- which isn't necessarily a bad thing, but it does eek up there on the highest levels of stress I'm willing to endure while playing a game.
Overall I'd rank it in my top 5 PC games of all time, up there with WoW, TF2, Diablo II, & Left 4 Dead. Related Designs (whom I've never heard of) managed to score a spot amongst Blizzard & Valve? Simply great.