Why? Because on the show Serena usually gets laid every episode and usually falls in love with 5 guys at a time, therefore being considered a slut by many real people as well as characters.
The second part of the nickname is due to the fact that the actress has great looking boobs (the reason why some guys watch the show, unless you like the "story"), which are at many times showing during the show.
*Note that Blake Lively is not being called a slut, only the character she plays on that TV show is under that nickname.*
Guy: That's why I watched it in the first place, lol.