I don't like 'safe'. I like risk and reward.
Players with little upside but also little risk (comparatively speaking) are what we would think are 'safe'. These tend to be average RBs on lesser producing offenses, but are bonefide starters. Clinton Portis is an excellent example. He's not the same back he was and the rushing production doesn't excite a person, but he is the clear starter and has put up pretty consistent numbers. He would probably head my list of low risk, low reward.
Of course, then you have high risk/high reward. Take Reggie Bush for instance. He's not even really the starter - but what if he does have a breakout year? The numbers he could put up in that offense...of course, he did have microfracture surgery...he could also give my team almost nothing if his body just isn't made for the NFL. But I'm not counting on him...I'm hoping for him.
Flip side - Addai would be a low reward, high risk. You know pretty much what his top potential is, and he'll likely produce it...although, he can only go down from there. And when the Colts use a high pick on a RB...not a good sign.
Then you have low risk/high reward. These are guys you get in the late rounds...they basically cost you nothing. Someone like Charles or Buckhalter. Usually, these are the guys termed as 'sleepers'.
I usually will assemble my draft board in basically that order. I want my projected starters to be guys that I'm pretty confident I know what they'll do, barring injury. Once I have my starters, I don't want to follow that up with a low reward/high risk guy...I want someone who may even be better than my starters, and I can get him really cheap. So I pretty much ignore the risk and look only at the potential. Once you've got your mid-round 'risk' pick in, then you can look for value among the low reward guys. These guys, because they basically have no potential for first round production, can slip pretty far sometimes. You can get a solid player way below where he should have gone. And finally, you have your late round sleepers which are 90% luck on whether you hit it big or not.
I think many owners, either knowing or subconsciously, follow some form of this pattern. It is why the person who selects Westbrook moans and whines the whole time he is doing it. He'd rather take a player with less risk, but the potential reward is so high, eventually you have to pull the trigger. This is the same owner that will then draft fewer sleepers and try to pick up as many low reward/low risk guys as he can.
But the difference between each owner is where they draw that line. How much risk is too much. How much potential does a backup RB need to be drafted before a starter? Would you rather have a backup like Donald Brown who may be useless to your fantasy team unless he starts, or would you rather have Kevin Faulk which will play every game but probably not have a single big game.
Each owner has to decide what is important to them - and for most of us, it depends on what round we are in and who we've already drafted.