Killing NPCs in Skyrim will not effect quests.

Killing NPCs in Oblivion caused an effect on the quests. However it's been confirmed this won't be the case with The Elder Scrolls V: Skyrim.

Bethsuda's Pete Hines explained about Skyrim's new 'Radiant Story System' which will add dynamic content to the game as the player progresses.

Quests, towns and random encounters will all be dynamic based on the previous actions by the player.

Hines Hines told pcgamer.de at Gamescom:

It also allows us to account for the player doing things in the game that might break a quest normally. You get a quest from a merchant and then you get a quest from the Dark Brotherhood to kill that merchant. We're able to put other actors into the role of the quest giver so that merchant has a relative or a spouse or something who steps in his role and you can finish the other quest that you got even though you killed the guy.

Pete Hines interview: The finer points of Elder Scrolls V: Skyrim