I'd like to see a more complex karma system, perhaps one that lets you, or the results of your actions, decide what is right and wrong.
The current Karma system seems a bit obsolete to me, I mean, I can't steal stuff from Powder Gangers that I've already killed without getting bad karma.
Karma is such a hard thing to decide what's right and wrong. Killing people is wrong. Unless they are evil. But what if you percieve them as good guys or fighting a good cause, or if you kill them because you enjoy killing them and not because it's the right thing to do? It's a very hard system to make. I'd say that every time you kill someone that fired on you first, you shouldn't get negative karma no matter what their karma was - you just defended yourself. You should not get positive karma though, as killing is still wrong. Maybe it was some guy who was too twitchy, just defending his family from wouldbe raiders and you responded to his fire and killed him because you thought you were being ambushed? That is just a mistake. Maybe if there was some option of shouting "don't shoot", put your hands up or something so that you would get to speak to him instead and therefore have a positive karmatic solution to everything? Even if it was raiders, they all shouldn't just have "shoot first, ask later"-attitude. I'd like some to ambush you, surround you and then at gunpoint say "give us all your valuables, you may keep your clothes you are currently wearing, a bottle of water and an unloaded, or we'll kill you on spot and... how do they say it, "pry it from your cold dead hands"?"
Later, your karma could also affect dialogue. If you've got good karma, you could get a good karma speech option, like if you are going to help someone in tears to find her family, you could say something reassuring and nice to her, that you promise to find them and the kidnappers will be punished etc. If you've got bad karma, you could say something evil instead. Saying evil stuff to good people freaks them out, which could be good for you in some situations, could be bad in others. Saying evil stuff to evil people could impress them, maybe you get some job you otherwise wouldn't get by some mob boss and getting ambushed by lowlife thugs would have the same effect as in Freeside where they back off if you have low karma.
All in all, karma should be actually worth something and both negative and positive karma should be worth it to you and whatever you roleplay.
On another note, if you have good karma and want to impress or infiltrate evil people, there's always a good speech skill, or rather, deception skill. Speech getting divided into Deception and Persuasion, deception working for all the [lie]-options (should be more of those), all the options where you can fool someone in any way, and also cheat at cards (it's a form of deception) as well as deciding how good your disguises are. Persuasion would be more like what Speech is now, talking people into seeing things your way. Deception and Persuasion is kind of like the Speech equivalents of Bad and Good karma. Although there is no reason why you can't play a conman with a heart of gold or a silver-tongued devil.