To be fair about the power levels of the 4.9L, all engines back then didn't make much power. My 1990's F150 inline 6 made 150 hp and my cousins 5.0L made 185 hp. Only 35 more hp yet it had more issues than mine. The 7.3L diesel made 180 hp in those years and the big 7.5L HD gas engine made 230 hp. I remember watching a power nation episode not too long ago where they modernized a 4.9L inline 6. With EFI and better air flow in and out, it made around 300 hp without increasing compression ratio.
There are also other inline 6 engines that are known for holding up to more power than V6 or V8 engine of similar displacement. Two prime example are Toyota's 2JZ and BMW's N and B series engines. The 2JZ is known for handling over 1000 hp at the wheels on stock internals and so far the BMW's are up to over 700 hp on stock internals. Primary reasons is due to their closed deck design (which is nearly impossible to do on gas V8's while keeping them cool) and their primary & secondary balance putting less stress on the crank and other internals.
In regard to the Ecoboost, as I mentioned previously, we have around 300 in our fleet and they get to 200k miles before we send them to auction. Many of them have an enclosed trailer hooked up to them 90% of the time towing upward of 7k lbs and we still get 200k out of the.
Do I think small turbo or NA gas engines (regardless of cylinder configuration) belong in an HD? No, the duty cycle of the HD trucks would create too much heat, however, they do have a place in half tons or even heavy half tons like my old F150HD that ironically had more payload than my Ram 2500. In the flip side, I do believe a large displacement engine, regardless of the number of cylinders or configuration, with a modest amount of boost or even N/A would be a perfect fit.
A large displacement inline 6 would likely not make more horsepower than a V8, but it would be easier to get more low end torque out of the inline 6 due to being able to fit a longer stroke. A longer lever(connecting rod) will always be able to make it easier to apply force to an object(crank shaft) than a shorter lever. You can get a V8 to make more low end torque, but you will have to make adjustments that would sacrifice top end power. The inherent design of an inline engine allows for a longer stroke while still being able to fit it under a hood. This is one reason why a V8 pushrod engine is better than a DOHC engine at making more low end torque. Due to it's design, the pushrod can have a longer stroke while still being compact and able to fit under a hood.