The "best" layout is very personal and depends on your preferences (inward rolls, outward rolls, alternation, even hand use or biased towards your stronger hand, etc.) and also your physical keyboard layout ("normal" staggered rows layout, matrix layout, staggered columns, number of layers, whether you use thumb key modifiers, etc.).
I use a version of AdNW (optimised for staggered vertical columns and thumb key modifiers, like ErgoDox, Truly Ergonomic and my DIY custom board) and can really see the improvement over QWERTY, especially in home row use. One thing which tends to irritate me with most alternate layouts, though, is the optimisation for inward rolls. I find inward rolls really awkward, outward rolls are much more natural for me, but there isn't a layout designed for outward rolls. So I go for layouts with more hand and finger alternation instead. I know my preference for outward rolls is an exception, though, as most people seem to prefer inward rolls. Just makes it hard to find a layout that suits me. <sigh>
I tried getting the AdNW optimiser to generate a layout for me, but I couldn't understand the instructions properly and have not yet been able to get it to run with my own optimisation criteria. Well, I'm quite used to my modified layout now, so I'll stick with that.