The big picture is insanity, more or less. Get used to the types of scenes you saw with Cassidy (the Irish vampire) and Tulip in the cornfield, because Garth Ennis (the original writer) has a hell of imagination and the series should be full of that type of thing (not to mention completely whacked out supporting characters, some of whom you got a taste of already).
There is an over-arching story regarding the invisible entity that entered Jesse towards the end of the show, but all of the little sub-plots they are (hopefully) going to weave in there are just as interesting and actually more fun than the big picture stuff.
It really helps that Seth Rogen is a huge fan of the comic and is the executive producer. They have made some changes to make the story more contemporary (the comics came out over twenty years ago), namely Tulip is now black and completely kick-ass and Jesse doesn't have a mullet (you may have noticed Tulip's comment about hating his haircut, a nod to the comics). Otherwise, it looks to be spot-on...especially Cassidy. Before he saw the show, Garth Ennis met the cast at a get-together and knew who Cassidy was before they even told him...that's how faithful his character was to the source material.
Really, really looking forward to more and hoping it will take off like the Walking Dead so's I can contribute to my retirement fund once the back issues take off in the collector's market, LOL.