Would Hand of Manos (with the lifeskill mastery artifacts offer +40 mastery and +1 luck) be a better overall combo to use to have more mastery than other mastery combos that offer +45? Wouldn't Hand of Manos simply be a better option bcause it covers ALL lifeskill categories... rather than having to perhaps make different ones for specific lifeskills?

You don't want the mastery only sets. There are sets which give you a combination of alot of stats, like

You can put these into Mastery Artifacts. For example, put Fundamentals of Cooking into Cooking Mastery Artifacts (which is BiS for cooking)

For Life Exp i would recomend using Delotia set with Life exp Artifacts (so you only need one set):

Thanks! I've got a few of these combos. I just got a paradise lightstone last night from a boss rush so I was looking into what I could use it for.