This is a good question, but difficult to answer. Southpaws have become more and more prevalent since the 80s, but most fighters only fight a couple or no southpaws in their entire careers.
Tough question. Mayweather is the best answer I can come up with. He beat Corley, Judah, Ortiz, Guerrero & Pacquiao. He did struggle with Zab early on, but I think that was more to do with the fact that Zab had faster hands.
Carlos Ortiz had great success as well. Kenny Lane (2 out of 3), Flash Elorde x 2, Teruo Kosaka and Dave Charnley
At heavy clearly Wlad. Yes Sanders blitzed him out but aside from that fight Wlad excelled and fought in an era that was southpaw deep. Tony Thompson 2x Chris Byrd 2x Ruslan Chagaev Sultan Ibrigamov Probably the deepest run of any heavy vs quality Lefties. He also just missed Michael Moorer when he lost to Eliseo Castillo and fought him.
Some great mentions already. Kostya's straight right hand was a cannon and he was great at keeping pressure on. Hopkins such a brilliant technician, so much variety in that right hand of his.