I cast and wind with my right hand. I tried left handed and especially in the salt would wind up with cramps in my hand. It was just to uncomfortable. I don't ever remember losing a fish because I have to change hands. Another reason is that if a right handed caster doesn't pull straight down while stripping line off the reel and the reel is set up for left hand wind, you will be pulling your line against the revolving spool instead of the frame and line guard. Prematurly wearing out your line. Most newer reel have an exposed spool rim.
About the upside down reeling. Those of us who fish bamboo will fight some fish with the reel on top to try to prevent the bamboo tip from getting a set. Learned this one the hard way.
Since I doubt any of us are using tippets stronger than our backing, If I think I'm gonna get spooled ( I Wish) point the rod at the fish and the tippet should break before the backing or any other knot in the system.
No matter how you set your reel the line should come past the line guard. Any other way you can not only damage the line but I've seen reel frames with grooves in them from the line.

Tom