I am currently playing through un-twinked with a fishyzon and am about to finish Act 5 Nightmare. My resists are going to be lacking a little bit once I make it to Hell and I have the runes to make both smoke and lionheart... however I am unsure which once I should make.
Since I have low physical damage the 20% enhanced damage doesn't do much but the +vitality and life is pretty nice. The resists on smoke are pretty insane though. Let me know what you guys think.