>However, what do you do if the lines can have different
>voltages and won't tolerate a high series impedance (>10 Ohms)?

You mean apart from why you need such flexibility ... ??

I guess you could use something like a bunch of DG201 type multiplexors, 
provided you kept things like the RS232 lines within +/-12V. Using suitable 
series TVS clamps should be able to limit input voltage excursions enough to 
protect them. 

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