In general? No.. There have been a couple that have made things temporarily interesting... I don't think it is a southpaw thing though. Floyd is smart enough to figure out just about any style, unless he is just too out matched with size and strength.
Simply No. All the Southpaws he's faced in his entire career he's only lost about 10 rounds total. He got hit with a good shot by Corley but turned right around and dropped him in the same round. It's a myth started by haters.
They just give him a better challenge than orthodox fighters. But since he's extremely popular and generally dominates fighters with ease, the challenge will automatically translate to struggle.