Here are a few ideas:
new setting-they already said that most likely it will take place on the west coast.How about the Boneyard?Or better yet the locations from Fallout 1/2,I think it would be incredible to experience that world in 3d.
bring back the karma system-They absolutely nailed the karma system in nv so why not bring it back?
Enclave-seeing as most of the fallout fans have only played the 3d ones,we haven't really seen much of the enclave.In f3 they were bad guys no question,but with the "grey" karma system in nv,maybe we cand get a new look on them.
The music-keep the vegas\western themed songs and bring some back from nv
What are your ideas?