2,2,2 v's 3,3 - space does indeed cost, but it needs to be weighed against the popularity of the config. If your competitors fly widebodies with 2 aisles and you offer a narrowbody with one, then your aircraft may not be so popular. Its a difficult equation, but given the choice for the same aircraft size I'd go for the 2,2,2.
I fly the 767 on shorthaul routes, and even though it has higher fuel burn than the 757 it does an excellent (profitable) job especially when you add in cargo. From various destinations we carry tons of the stuff. The Airbus 320 family cannot do that, the 757 is limited in that respect and the 787 is too big. There is a gap and it will be interesting to see what will fill it.
The great power of the 767 and the 757 is their flexibility - something the 320 doesn't have. Its up against weight limits and range limits and cargo hold size. For some airlines this isn't an issue, but when the 75 and 76 leave the fleets of some airlines, then something will have to drop. It depends where the airlines want to place their risks - fuel burn or lack of flexibility.