Another issue for a commercial aircraft with pairs of engines in a pod would be certification requirements in case of engine failures. I don't know if any standards currently exist, but I could easily see that the regulators might hesitate to count those two engines as completely separate. Just think if you had a fire in one of them - could you really expect not to shut down the other engine in the same pod?
Also, as I understand it, the B-52 experience (admittedly built to rather different standards) is that the failure of the second engine in the pod is more-or-less assumed (not that it always happens, of course), and the aircraft is flown more like a quad.
You'd probably be able to certify an aircraft with four engines in two pods on more-or-less that same basis as a twin, but then you'd end up with the worst of both worlds - a quads fuel consumption, and a twins need for extra power. You might find a situation with an extremely large aircraft where the lack of suitable single engines might make that a practical option (for example a 2.5 million pound aircraft with eight GE
-90s in four pods). Much smaller than that, and you could just build an ordinary quad.