But after the Indianapolis Colts name Stanford's Luck with the first pick and the Washington Redskins follow by claiming Baylor's Griffin (nicknamed RG3) as the second overall choice, the next 30 first-round selections are a guessing game.
"One and two is a foregone conclusion but I think from there on there's gonna be a lot of 'Boy, that's a shock,'" former longtime Dallas Cowboys player personnel chief Gil Brandt told Reuters. "This is a draft where there's a lot of players that look a lot alike."
The annual draft of elite U.S. college football players is the lifeblood of the NFL, where teams replenish their rosters and address weaknesses in a rite of spring that gives all clubs reason to hope for improvement.
The first round of the draft takes place Thursday at Radio City Music Hall in Manhattan, with rounds two and three to be held Friday and the last four rounds coming on Saturday.
Third choice in the opening round is held by the Minnesota Vikings, who are entertaining offers from other clubs keen to move up in order to ensure getting their preferred player.
Following Minnesota are the Cleveland Browns, Tampa Bay Buccaneers and St. Louis Cardinals.
The Cleveland Browns (No. 4 and 22), Cincinnati Bengals (17, 21) and New England Patriots (27, 31), all possess two picks in the first round.
Other highly regarded prospects pegged to go early include offensive tackle Matt Kalil (University of Southern California), running back Trent Richardson (Alabama), cornerback Morris Claiborne (Louisiana State University) and wide receiver Justin Blackmon (Oklahoma State University).
The next quarterback likely to be taken after Luck and RG3 is Ryan Tannehill (Texas A&M), who played wide receiver his first two years in college.
Tannehill, who had only 19 starts at quarterback, has shown a strong arm and a natural aptitude for the position.
"I learned a lot about the game and a lot about playing quarterback by playing receiver," Tannehill said. "In my 19 games I felt I proved myself and got a lot better each game. And I feel like I'm going to continue to get better."
NFL Commissioner Roger Goodell, who along with the prospective draftees was attending a charity event promoting physical education for school children, said he met with the 26 players who had come to New York for the draft.
"I met with them in three separate groups," Goodell said.
"It was an open discussion. It was more about how to enjoy the next couple of days. You know, this is a dream of theirs."
Asked if there was any mention of the controversy over the New Orleans Saints' bounty program that paid players for knocking opponents out of games, Goodell said he spoke to them in more general terms.
"In my office I have an NFL shield up (on the wall). I pointed to that and I said, 'Everything we do has to reflect well on the integrity of the league and that shield.
"And everything that you do, everything that I do and everything our clubs and coaches do has to reflect well on that. It's our responsibility to improve the integrity of the league and make it better than when we came into the league.'"