I still can't make the pick, but I'm pretty sure we're dealing with a fiercely competitive and intense fight... No 8-4 for either side...
In other sports, defense > offense, but I've seen Mayweather's fights against southpaws and he's not as great. To be his usual accurate self, he's forced to pressure southpaws, thus not as comfortable as he is against orthodox stances. And pressuring Pacquiao is almost asking to get hit with something you don't see coming.
The real key to getting the W against Mayweather isn't unlocking his defense, it's shutting down his offense. His close fights (or where he's lost multiple rounds) came when his offense was shutdown or not as efficient on offense and then being outworked or landing one clean punch in the round (De La Hoya, Castillo, Mosley, and Judah).
The Judah fight is one of the best examples because he shutdown Mayweather's offense in the first 4, but only landed a few clean punches per round himself. As soon as Mayweather got his offense going (a Mayweather adjustment/Judah mistake, but another story), Judah's offensive numbers went down.
As Mosley showed and Naazim said, the blueprint is out on Manny. Just constantly moving to Pacquiao's right (without landing counter punches) slowed down his offense enough to reduce his output and accuracy. Mayweather has the same problem but opposite side (when you stay or circle to his left), but it hasn't been exploited much and he's made the necessary adjustments to it in the past.
Tossup fight, but I am leaning toward Mayweather, since I think he can stick to the right game plan enough to escape with the W.