You're right about the long runs, but I'd argue that a PEX remote manifold, if located/done correctly, should improve your delivery system even in those cases. As I said in the beginning, easier to do in new construction, mostly difficult, and usually expensive to effect in most retrofits ... which is why it isn't often done, and IME results in the biggest cause of user dissatisfaction with tankless installations.
Close to the endpoint (your "right at the tap") is pretty much how Europe has operated for decades, and very successfully. Pumps and a loop system, if properly implemented, also seem to work very well, although I haven't built one that way personally.
=======
I could see using a low temperature preheat (maybe NG or solar) to take the edge off the initial water heating and then a small (maybe electric) booster to give the final temperature at the faucet. Probably too much installation expense though.
I have many of my runs disconnected from my hot manifold to keep more frequent circulation going in the trunk runs. I was waiting so long for hot water it was painful. I want to put my air handler on the end of that run yet, to keep hot water close to faucets, except it will not help in the winter and the legal limit of 60C makes an upstairs warm-up each morning a little too lengthy. I did add it to the feed of the manifold and that cut a few seconds off the time delay. I still have access to most of my PEX as the basement ceiling is removable tiles or open. Not done experimenting yet.
The PEX really puzzles me over my old house copper system. I have less length to the farthest faucet, and the PEX is supposed to be smaller ID and it still seems to take double the time the copper house did for hot water to hit the end faucet??? Maybe I am just watching too closely. It also seems to cool off much faster than copper pipe so you start with room temp every time. I was thinking it should be the other way around. Meanwhile a neighbour installed all copper and a circ pump and has hot water within 2 seconds anywhere. GRRRRR...