1) QB is the new everything. The guys in your league who have Aaron Rodgers, Tom Brady, Cam Newton (yes, he qualifies, he's not going to stop being their goal line back) and Drew Brees have a huge advantage. Just about every week. And no, this doesn't mean that you can't compete with them, but if you don't have one of these guys, you should be prepared to get a second guy and play matchups all year. Even with ostensible every-week starters like Matthew Stafford, Matt Ryan, Philip Rivers, Either Manning or Tony Romo. The difference between Tier 1 and everyone else is just that great. (And yes, I see you, Lions Fan who thinks Stafford is all that: your man isn't going to stay healthy this year. Sorry.)
2) Before you go hard after a RB, predict his team's won-loss record. Unless your name is Steven Jackson, a long-term losing record means that your guy isn't going to get touches in the second half of games, and maybe not the second half of the year. (The covering caveat: if your guy is tolerable at pass protection and the team has a skittish young QB they've paid too much to see broken.) There are few things less fun in fantasy football than watching your early round reach stuck on the same point total because the conditions of the game have taken away his chance to contribute. If your RB is on a team that's a double-digit 'dog, you probably have better options.
3) Like position in poker, situation is important... but it's not a substitute for talent. I've seen Ced Benson touted as a strong RB2 in all kinds of places in the past month, and, um, well, he isn't. He's freaking Ced Benson, for heaven's sake, a plodding 3.5 yards per rush guy who doesn't catch passes and had *real* problems not fumbling the ball last year in Cincy. He's also on the wrong side of his career arc, on his third team, with a criminal record. I get that Green Bay is making him seem shiny and new right now, and they may seriously think he's better than James Starks, but he's not turning into a 300-touch guy who will salt away Packer wins by grinding out 100 yards in put it away time. He's going to be part of a committee until they wake up and realize he's Ced Benson, and they have other opptions. And he's just not that talented, really.
4) Wide Receiver is deep... but WR1 is not. Nearly every team has a de facto top dog, and if your league starts 3 guys, that means you need at least two of those guys on your team to achieve parity. And since WR is less injury prone than the other skill positions, those picks are going to hold value more than many RBs. If you've got multiple guys that are working the slot or strong 2's, you don't have a good situation. Period.
5) We don't really know what the real deal is at tight end yet. You didn't win your league last year without Rob Gronkowski or Jimmy Graham, unless you had Tony Gonzalez and a ton of help at the other positions... and I know that the temptation when watching these behemoths post up in the red zone is that you've got to have one of your own, like top-tier QBs. But the NFL has a funny way of killing fast-acting trends (remember how every team had to have the Wildcat, or their own Wes Welker clone?), and TE throws in the red zone aren't without peril, given the tight quarters and turnover potential. Put it this way; if Bill Belichick decided to use Gronk as a decoy for half of the year and just run the damn ball in close, he'd probably score as much as he did last year... and your first-round reach is going to be a lot less dominant than expected. And it's not as if Brees in NoLa isn't prone to spreading the wealth.
Personally, I don't rank Antonio Gates very far beyond Graham and Gronk this year, and I also love me some Aaron Hernandez and even Jermichael Finley, last year's gotta have it TE. And I also don't completely discount the idea that a deep reach move like Kyle Rudolph or Coby Fleener might provide Tier 1 value, or that Brent Celek or Fred Davis might have a career year. You aren't going to leave your draft or auction with known superstars at every position, and until there's a second year of Tight End Domination, I say make it a depth play.
Oh, and if you are valuing kickers or defenses as anything but a basic crap shoot, you are spending way too much time on your rankings. Throw a qualified dart (kickers in domes with pinball offenses, defenses with pass rushes in weak divisions) and get on with your life.
Finally, here's the guys that I like more than most... At QB, it's Russell Wilson, Jay Cutler, Matt Schaub, Eli Manning (too much regression noise -- he'll be undervalued like usual) and (the horror) Nick Foles. At RB, go a little harder for Ryan Mathws, Doug Martin, Donald Brown, Peyton Hillis and Michael Bush. For WR, I'm all-in for DeMaryius Thomas, Brandon Marshall, Brandon Lloyd, Jeremy Maclin and (dice roll time) Kenny Britt. The TEs are above.
And the guys I'm staying away from are... At QB, Brees, Peyton Manning, Romo, Ben Roethlisberger and Michael Vick. For RBs, it's Matt Forte, Marshawn Lynch, DeMarco Murray, Ahmad Bradshaw and Shonn Greene. TE stay aways include Gronk (too expensive), Gonzalez (he's got to get old at some point), Jacob Tamme (too many other targets), Jared Cook (eternal tease) and Vernon Davis (they added WRS, and QB Alex Smith is going to look wide this year).
And that, folks, is that. Have a great draft...