IMO, it depends on what you like. The Southard has a much larger blade when open, and is much smaller in the pocket when closed. On the other hand, the Domino flips better, has that funky Spyderco tall bladed design and better access to the hole, and is large-handled to the extent that it may be bulky to carry, but it's also very comfortable to use in a variety of grips when open.
If you're into more normal designs, go with the Southard. If you really dig the short, wide blade shape, go with the Domino. The Southard is more normal-ey and the Domino is more Spyderco-ey, if that makes any sense.
Personally, I love the Southard and can't warm up to my Domino at all, but as this thread shows, plenty of people feel the other way around.