sword and board, or a 2-handed?
wand and offhand focus or something else?
It really all depends on your build, up to night mare I use a very fast attack main hand and a focus to build Essence quickly - as a blood build to maximise its 3 Hemo’s and then a surge, beyond nightmare, Armour and resists are just too important where a Shield will play a more important role I am guessing (Not quite in Hell yet, DPS more than enough to kill, its the elites one shotting me - But this was in Normal gear, Im now just farming gear to get up to sacred and then socket gear etc before going back to trying the Capstone in hell again).
If you looking for damage, just switch to whatever gives you more damage. If you looking for stats, go for wand/sword & focus. If you looking for survivability, go for a shield instead of a focus.
One downside with 2-handed is that you have one less aspect
I am using a 2-handed because of the damage but now I need an extra aspect so I have been looking for a while to replace it with a sword/wand and a offhand.