For my style of playing (rhythm and lead combined - Hendrix and SRV style) the 50's style works best - especially with humbuckers. I can strum my guitar with the volume down on the guitar and get an almost acoustic sound. When I turn the volume of the guitar back up I can get the lead tones I like. When I play rhythm on a guitar that is not wired 50's style it seems muddier, in my hands, then when I'm playing rhythm on my own guitar.
For me, the 50's wiring is all about the rhythm tones.