Lame answer: you have to try a bunch of lines and figure it out for yourself...it largely has to do with personal preference. At our level theory is somewhat less important. Most of our opponents deviate before any cutting edge mainline stuff would come into play.
More interesting answer: I have tried lots of stuff, and like the mainline slav and Queen's Gambit Declined.
Although the mainline Slav allows a good player to get a draw somewhat more easily if he's so inclined via the exchange variation, you get equal space and esay development. If white wants to get an advantage he has to ruin his pawn structure to do it, giving you endgame odds. Check Vigus' book from Everyman. Play the Slav
Next up Queen's Gambit Declined. Awesome, Sound, Great History, employed by every world champion, and even the Exchange Variation with Nge2 isn't as scary as we thought anymore. ALso great books on it, MacDonald Starting Out: Queen's Gambit Declined, Chris Ward: Play the Queen's Gambit, John Cox: Declining the Queen's Gambit. Cox's book also covers the Catalan, bonus! These are in ascending order of difficulty and theoretical content. Sadlers book is excellent too, great for ideas and history, maybe start there, it's a little outdated. If you like Descriptive Notation, Chess from Morphy to Botvinnik by Imre Konig has a really great chapter on the Queen's Gambit Declined's History, and also all the other 'Center' Openings like the Ruy Lopez, but not the Slav, it's really outdated. But awesome. Also, Queen's Gambit Declined works against English and Reti, double bonus!
Then there's Nimzo-Indian Queen's Indian systems...these are fantastic 'Cadillac' Openings, but they cede space in the center early. In exchange they create imbalances early to create a winnable game for blackin every variation if he chooses, while still being solid. There's a lot more to learn here than the other examples, but they might be the best choice. You have to find out for yourself.
EDIT: Ward's book is an opening book for white. Sorry!
I usually answer with d5. Then what? Should I learn the semi Slav (or perhaps Slav?) what is the easiest way to handle (as black) white's d4 opening? Stwils. (I always open with e4 as white.)