A way to integrate Karma a bit more thoroughly, as well as make certain decisions have a permanent effect on Karma as well as Reputation.
The basic framework would be that some factions would be designated as "Good" some as "Evil" and most as Neutral. Achieving a positive Reputation with a Good faction would reward a small one-time Karma bonus (say 25/50/100 for each respective rank) while negative Reputation would reduce your max Karma (200 points for Villified, 100 for other negative reputations). Evil factions would reduce max Karma for being Idolized (100), but you would receive no Karma bonus for being Villified by them (that would be too easy). Being Villified by a Neutral faction would also reduce max Karma (100).
Goodsprings, Freeside, and the Followers of the Apocalypse would be Good, as the ways you raise or lower your reputation with them are the least morally ambiguous, and Caesar's Legion and the Powder Gangers would be Evil. The effect of this would be that you couldn't become beyond moral reproach just by being Idolized by for your do-gooding, but you could end up being irredeemable if you wrong enough factions/settlements.