I don't think the He 177 would replace B-24 and B-17 usage. While the lanc seems to be used purely for utilitarian reasons, the B-24 and B-17 especially seem to be used more for sentimental, and historical reasons.
Additionally, if the B-29 and Me 410 are any indication, the defense will be nowhere near as strong as it is on paper. Those remote turrets really do seem to be made of glass.
And given the historical weakness of the engines, I suspect it would be even worse than the B-29, and likely would be unflyable with one engine.
I imagine it would be rather like a larger version of the Tu-2 in some ways. Amazing on paper, good in reality, but still a tiny bit underwhelming.