Jimi Hendrix was left handed, played a right handed guitar "upside down", but he had them restrung for a left hander.
There's an eyewitness account of Hendrix, handed a righthanded strung guitar, playing it both left and righthanded - well.
Left handed guitarists, like left handed baseball pitchers, seem far more frequent on stage than in life. For some reason.
On tunings:
A fair number of Primitive guitarists use alternative and idiosyncratic tunings - Alex de Grassi, one of the old Windham Hill guitarists, at one time I think was approaching tunings as in Indian Classical Sitar music, ending up with his compositions and tunings almost in a one-one relationship and extensive elaboration within each composition derived from the tuning. He was very fast at tuning on stage.
The Hawaiian guys are all "slack key" players - here's a really beautiful tuning from that island: CGDGBE Try it.
For an education in tunings, John Fahey. Also an education in guitar music (start from the beginning). He used open C tunings more than most do, getting the third outside "where it belongs"- such as in the album "Requia", the "normal" tracks. One of them is in this tuning: CGCGCC. (this one iirc
) If you want to hear what CC is talking about in post 22 above, especially with regard to the blues rather than Celtic, early and midcareer Fahey will provide. (the album photo is flipped - he played righthanded. And nobody makes a pick like those any more: Herco Medium Gauge 60, hard celluloid with the belly molded in. Good luck getting that sound with anything else).
My difficulty with alt tunings is that they interfere with social playing - but like a lot of players, I've picked up a couple of things that require a weird tuning and I'm too fond of them to drop the tunings. So I end up putting more stuff in those tunings, and pretty soon whole chunks of my repertoire require that I retune the guitar. Then they aren't at hand in company. So I've learned to put everything I'm going to play with certain people in one tuning, by discipline. With the Irish, say, I stay in Drop D (DADGBE, - most Irish players in my area use DADGAD). But that cuts most slide playing out of the Irish, where it often fits well. Also, there's a lovely, haunting way to play the Irish tune "The Morning Dew" in a high D drop (EADGBD), and I wish I'd never come up with it. Damn.
And I'm not the only one. Almost every guitar player I know has this one tune in this one tuning that they can't discard. If you're Harvey Reid, say, and in a moment of divine inspiration you saw how to tune a guitar to lay"Fur Elise" by Beethoven into it, are you ever going to give up that tuning? (No) How about Martin Carthy's "Cymru"? Duane Allman's "Little Martha"? (not that open D is all that odd a tuning).
I started changing the tunings as soon as I started playing the guitar. No regrets. But they are something of a trap. The best lesson was how to play a standard tuning as if it were an open tuning, say E minor - how to get that sound.