The one issue you didn't mention is how the lowered flow resistance of the heatercore affects the overall flowrate. The increased flowrate with a single pass heatercore will reduce the thermal resistance of the waterblock. The thermal resistance of the waterblock is much more dependent on flowrate than the heatercore. (over the range of flowrates typically seen in watercooling systems.)
It's worth considering the relative flow resistances of the heatercore and waterblock though. If the waterblock is much more restrictive than the heatercore, then reducing the flow resistance of the heatercore by a factor of four won't have much impact on the flowrate through the system.
Aside from that, it looks like you've considered all the relevant issues.
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