I think that is potentially one of the big advantages of a mileage-based fares system. It would enable this because there is no need for anyone to calculate in advance what the fares between any two stations are. To take your example, you want at ticket from MKC to Newcastle via Liverpool? It gets priced up automatically on the fly. Add the miles from MKC to Liverpool to the miles from Liverpool to Newcastle to get the total mileage, and then calculate how much a ticket for that many miles should cost. There is never any possibility of a ticket between any two places not being available because you can always calculate how much a ticket for that mileage should cost. It doesn't even require the cost to be directly proportional to the distance: Any mathematical formula will work just as well (for example the power-law formula I suggested some way up-thread, which causes cost-per-mile to go down for longer journeys).
I could see value in something like this:
1. Anytime fares based on a mileage based system with some adjustment (using "tariff miles" as Europe uses "tariff kilometres", so some rural lines might be priced down and the ECML might be priced up, say) using rather than a straight "per mile" value a curve, with increasingly longer journeys being cheaper than shorter ones and probably an absolute maximum Anytime Single of around £200 at current prices (by way of that curve tailing off at that cost). This would probably require the WCML Anytimes to reduce a bit but would keep London-Edinburgh about the same. These would be specifically routed in the manner German ones are, but a more expensive one would always be valid via a cheaper route.
2. Off Peak fares invalid for being on a train between 0430 and 0929 across the network* and being calculated as a specific discount, maybe a third or thereabouts. This would be higher than a lot are now but the validity is much greater, and they could be combined with Advances to keep the cost down given that most people know their outward train time even if they don't know their return.
3. Advance fares priced on a market basis but on a "per vehicle journey" basis, so no through fares to exist. The approach to these to change as was once proposed so you don't need to split them, i.e. each piece of the journey is priced based on the quota for that piece.
4. Break of Journey always permitted (as this system would have very few anomalies).
5. All fares priced as singles, though you could do Day Out Returns for Anytime+Off Peak (no need for Anytime for the way back, almost nobody would do a day return and want to both go out and back before 0930!) and Off Peak Day Out Returns for two Off Peaks.
6. No admin fee for changes, just the fare difference if the ticket is an Advance, thus if you want to change your return day on a walk up fare this is free of charge, but it avoids the ticket re-use fraud that is why the railway doesn't like period returns.
* Maybe except Sleepers, but to be honest given the specialist nature of these having them as an entirely dedicated fare set may be better, and single-fare pricing avoids this being an issue.
Booking engines would cobble the journey together out of those and issue against a single itinerary and possibly as a single coupon (though split coupons are for e-tickets sometimes actually easier!). Like with many of the planners that sell European tickets one could tweak with the options for different legs of the journey, such as taking a First Class Advance for the long distance bit but flexible singles for local parts of the journey - I often split to do this but it could be part of the core offering.
It's not perfect and some people would pay more (and some less) if we wanted to do it on a revenue neutral basis (as we'd have to - revenue negative won't** be accepted by the Treasury) - but it seems a fair hybrid and allows market based pricing as well as reasonably affordable walk up options.
** Or maybe it might. With the anomalies in it resulting in oddly low fares if one makes a combined rail and Tube journey, Project Oval can't not be massively revenue negative at the moment and I remain amazed those anomalies remain unfixed.