From a real football perspective, Andrew Luck is the safe choice as the number one pick in the NFL Draft. Non-traditional quarterbacks do not win Super Bowls. Period, exclamation mark, end of story. Tactical mastermind, drop-back passers win Super Bowls. Based on the history of the league, a QB like Luck is more likely to win a Super Bowl at some point in his career. He is probably also somewhat less likely to suffer a rash of injuries.
From a fantasy perspective — Robert Griffin III will likely be the more attractive option and the only rookie QB I would consider drafting in fantasy football — in the late rounds of a deep league. Griffin has the potential to be Cam Newton 2.0, only more likeable and smarter. He was an extremely accurate passer in college and has the potential to rack up yardage thru the air. He too has the added advantage of potentially relying on his legs when the friendly skies are not so friendly. As a rookie, when things will go wrong frequently, he will likely make electric plays with his legs, keeping his fantasy production a bit more consistent than most rookie QB’s. In Washington (presumably), he will be surrounded by better talent than Luck in Indy. Unfortunately, what he won’t have is Steve Smith. Carolina’s pocket-sized dynamo used to make Jake Delhomme look like a Pro-Bowler. Smith nearly single-handedly led a rookie QB to ridiculous heights. At present, Griffin’s most likely landing spots lack threats like Smith.
Also, keep in mind that Cam Newton was the exception, not the rule. In fantasy land we are all Cam-gaga because what he did was unprecedented. No rookie had ever had a season quite like that and its difficult to see two rookies doing it in back-to-back years. The two events are independent, but still unlikely.
Personally, I would be very wary of taking a rookie QB in the draft — even after riding Cam Newton from the waiver wire to the title game in one league. However, if he is available late, you might consider taking a chance on Griffin and seeing what develops.