I set my S1's at 256 as what is recommended and is also what I have had the most success with.
Yes difficulty can make a significant difference, especially if a pool sets it automatically or has a very low default difficulty setting.
Since the S3's are about 2.5x faster than the S1, then I'd say a difficulty 512 would be a good logical place to start; 200 x 2.5 = 500
Where 200 is the max speed of a unit at 256 difficulty; I never don't overclock something.
I'd also try over and under 64, 128 & 256 differences to push the envelope and get that extra bunch of satoshi a day for doing nor spending on anything else