I know there are a lot of IP's out there that start in different media(Game of Thrones, The Walking Dead, etc) when they switch to TV that they try to follow the source material, in this case the Sookie Stackhouse series by Charlene Harris, faithfully but eventually take a turn away. My question is how far into the series do you need to watch before the switch actually occurs?
One of the biggest (I consider) is right at the end of Season 1. Lafayette is still alive. He dies in the first book towards the end and is actually the body they find in Andy's car at the end of the season (Which isn't revealed until the second book).
Also, there is the lack of the addition of the Brain Damaged Vampire Bubba who is actually Elvis in Vampire form who was damaged due to an overzealous vampire fan of his, working as a morgue attendant.
While the series itself keeps a bit of the overall plot elements of the book it is on (currently, we are on book 5), they have detracted a lot from the book at this point.
For example, Maryann, the other antagonist for the second season, was played up much more than she was in the book, where the whole plot revolved around the disappearance of Godric. Upon returning to Bon Temps, they find the sex party has gotten out of control (headed by Castillo, renamed to Maryann) and Bill and Eric have to clean up her mess and she leaves. There is only a hint of her relationship with Sam and he is not the main focus of her deeds in the town. This is also the same events that kill Lafayette, as I mention earlier.
The list goes on but I think I have made my point.
I would like to add a bit to TylerShads answer...
Another difference is Tara, in the books she is wealthy and owns a clothes-store. Bill is very far from King or a Vampire-leader in the books (unlike Eric, who is at least Sheriff in both). Other characters too are quite different in the books than in the show - or at lest diverges.
The series have taken elements and scenes from the books - along with more or less the overall arch (like Sookie ending up with Eric) - but the books are more self-contained. E.g in one book Sookie is at a vampire-convention and meets someone who can also read minds... in another, she gets involved with werewolfs... In the books things are resolved once and for all and the characters are not heard from again, while in the show the characters lingers and new issues pops-up.