Ken, If I understand what I think you are saying, I think you'd need to look at sequential installation of twin turbos, not an easy task or packaging, OR, if they make them, a variable vane turbo set like the diesels use. I am not sure if they hit the gas engine market for the boost levels and RPM though. (Although my Cummins hits 24 psi day in, day out and I have 130K on it, bought it new). I do not know if ant Holley ECM does that to that level
My take then on the decision of stroker vs no stroker is really based on turbo volume, if you can get there in a street designed turbo that acts like a mass produced engine daily, with available parts, go big inches, if not, that 427 will still be making some big numbers anyway. With a street blower, we saw 1.69 hp per cid with no end in sight for a peak, with 8 psi. That'd be getting into some very big numbers with 14+
So the alternative is to can the crazy sequential idea and go for the smallest turbo pair that can feed the engine at a predetermined RPM, I bet there is some crossover point where the cid and turbo size makes sense to allow some low end boost but still behave well on top, or even toss the low end idea in the trash and use it to be able to launch the thing. It'd drive nice with EFI so you may not even notice there is a "loss" of low end
The other things now becomes injector requirements, when you go a combination of not big and big boost, a double injector, or additional injectors somewhere become helpful because when you size them for the big boost, they get sloppier down low. This would likely be compounded by the E85
Each of those makes the smaller engine a little "easier" maybe not easy, but lots of LS motors to look at for lessons learned at that size.
The last one is cam requirements, one thing I learned from my last unnaturally aspirated motor is, good heads plus forced induction makes a baby cam almost too big duration wise but still needs lift to use the port, great heads like Jays, probably even more so, which means you get into a lobe design challenge. I chose not to use as much lift as I should have for stability, but you may get into a point where you'd need a solid roller. I don't love the idea of a solid roller, but depends on what you need to do with the lobe
I am not getting that fancy, but collecting parts for my next one and I think it's likely going to be a 505-508 EFI hyd roller, ported TFS, ported Victor, with an intercooled centrifugal system. Jay's heads would be better, but it's likely going to be silly as is and more of a weekend cruiser than a drag car