Reputations in New Vegas were just really frustrating to me. It always seems off to me that the Legion would send an over-powered death squad after anyone who dipped into Shunned rep with them, and then of course killing the death squad would lower your rep even more. And locking us out of quest content based on faction rep might have worked for NV (the jury's still out on that one), it's antithetical to the open-world philosophy Bethesda approaches their games with. Karma suffered from different problems - in 3 there was no real reason for us to be evil and in New Vegas it was just arbitrary who was considered good, neutral, and evil - and while I'd say reputation is too important in New Vegas, karma just isn't important enough in either games.
For karma, I don't even want a karma metric as much as I want a reason to choose neutral or evil. Getting the truly good outcome in a quest should require extra steps, more work, and even risk betrayal; it should be hard compared to staying neutral, and less rewarding (in a materialistic sense ) than being evil. The good/evil outcomes of specific quests should reverberate throughout the world, changing what kinds of random encounters we see, or the choices we can make later on down a questline. A karma metric would help for how NPCs react to you and whatnot.
For reputations, I think they'd be better served to use something similar to how Skyrim's holds tracked regional bounties and thaneships. Each faction would track crime separately, and disguises would hide that criminal record until you committed another crime. Okay really, just don't lock us out of content and send ceaseless death squads to kill us for dipping into the negative territory.
Of course, my guess is that karma and reputation won't exist as metrics in Fallout 4; which isn't to say we won't get complicated political relationships and moral choices. Incidentally, we weren't shown any sign of karma/reputation in what we saw of the Pipboy menu, but that doesn't instantly mean they're no longer there. But I think Bethesda could really do a good job of tying in karma and reputations with their Radiant Story system.