Firstly, I'd say don't let perfect be the enemy of good; there may not be a perfect system, but Reddit back when I used it was pretty good 80% of the time, until you got to the big memey subs. There's an additional bonus here, in that activity can be seen. At first I was a little apprehensive but now I think I'm on board with it, so sock puppets can be tracked.
I don't think individual karma ratings should be used to weigh up votes across the board, because simply put, a user shouldn't have a bigger influence just because they got more Internet points.
I think the basic premise of all this up voting and down voting should be that it's a form of crowd sourced moderating. Users letting other users know what was interesting and what was detrimental to the conversation. I've seen proposals like giving votes more context (eg a funny vote, like Steam reviews and Ars Technica's forums), so that might help shape the quality of the crowdsourced opinions.