The end stops can be set to accommodate both wheel sets, as long as catastrophic derailleur into spokes is prevented.
Di2 will only shift as far as required to shift so if you change wheelsets and trim to that wheelset, there is no reason for Di2 to send derailleurs past the sprokets, in fact, many Di2 bikes have never had their endpoints set and rely totally on the trim to stop overshifting.
If your cage is that close, then the hanger is probably bent and if you run different size teeth on each cluster, that will shift your trim as the cage is no longer swinging in plane with the wheel and may be you total problem or at least a significant contributor.
Align hanger, set end stops to allow full movement on both wheels, trim to each wheel when you fit it.
This is only a couple of button presses so could not really be considered too onerous to change a wheel.
The introduction of 11 speed caused a bit of a tizz with hub makers and many of them increased the overall locknut dimension to try and claw back a little lost wheel strength caused by the extra dishing required to fit 11 speed.
Zipp increased theirs by .8mm in the first versions of 11 speed for this reason.
Discs generally did not suffer, being thinner, so stayed true to standard locknut dimensions.
So depending on exactly which models you have there may be a difference in overall locknut to locknut width.
Variance in wheels here is not uncommon as with some designs (not Zipp), simply adjusting the bearing preload will alter the locknut dimension, so get used to it, it is common and expected to have to trim gears to a different rear wheel, even if the hubs are identical model.
That's just how it is.
But there is nothing preventing you from running both wheels with only a small trim in required.
If you trim in the middle of the cassette there is no chance of derailleurs going too far and rubbing or dropping chains until it is aligned.
There should be no need to run any spacers on any 11 speed road setup on any road wheel apart from those using the thinner MTB cassettes.
Di2 will only shift as far as required to shift so if you change wheelsets and trim to that wheelset, there is no reason for Di2 to send derailleurs past the sprokets, in fact, many Di2 bikes have never had their endpoints set and rely totally on the trim to stop overshifting.
If your cage is that close, then the hanger is probably bent and if you run different size teeth on each cluster, that will shift your trim as the cage is no longer swinging in plane with the wheel and may be you total problem or at least a significant contributor.
Align hanger, set end stops to allow full movement on both wheels, trim to each wheel when you fit it.
This is only a couple of button presses so could not really be considered too onerous to change a wheel.
The introduction of 11 speed caused a bit of a tizz with hub makers and many of them increased the overall locknut dimension to try and claw back a little lost wheel strength caused by the extra dishing required to fit 11 speed.
Zipp increased theirs by .8mm in the first versions of 11 speed for this reason.
Discs generally did not suffer, being thinner, so stayed true to standard locknut dimensions.
So depending on exactly which models you have there may be a difference in overall locknut to locknut width.
Variance in wheels here is not uncommon as with some designs (not Zipp), simply adjusting the bearing preload will alter the locknut dimension, so get used to it, it is common and expected to have to trim gears to a different rear wheel, even if the hubs are identical model.
That's just how it is.
But there is nothing preventing you from running both wheels with only a small trim in required.
If you trim in the middle of the cassette there is no chance of derailleurs going too far and rubbing or dropping chains until it is aligned.
There should be no need to run any spacers on any 11 speed road setup on any road wheel apart from those using the thinner MTB cassettes.