I almost always prefer to connect in Europe vs connecting in the US. FRA isn't my favorite airport, but I'd take it over EWR any day.

Also, with regards to this, bear in mind that connecting in Europe makes bringing back duty free easier. You won't save much money, but the selection can be outstanding and worth lugging a bottle or two of something nice back home.

As to comfort, neither one will win any prizes, but I definitely think that LH TATL Y > CO Domestic Y. I'd rather increase my time in the widebody if it saves me time in a CO 737.

That being said, I would not hesitate to take CO if it were even marginally cheaper or if the LH fare only gave partial mileage credit.