Measuring high voltages, just use a bigass divider, no worries. But measuring small voltages (or currents) at high isolation? Digital conversion followed by fiber-optic is about all you can do.
Currents can be measured in isolation, using enough turns of wire around a Hall effect sensor. These are usually direct reading (no core, ~single turn) for 10-100A+ sensors, and use many turns (and a core) down into the single amp range. They aren't usually made for, like, single mA or less, but the principle might be applied.
If you need to sense the current in a bunch of common anodes, consider flipping the sign. Use negative ground. For example, CRTs were often driven either way: first, oscilloscopes needed the deflection plates (and face) at ground, so the electron gun cathode was operated at -2kV or so. Any control voltages (referenced to the cathode) were either generated in place (e.g., high voltage pots for intensity and focus), or coupled using capacitors (AC coupling), or more complicated methods. (The typical Tektronix "Z axis" coupling used an entire additional HV supply, purely as a series battery to the CRT grid, so intensity could be controlled with DC rather than AC coupling.) Magnetic deflection CRTs (e.g., almost all TVs) used significantly higher voltages to achieve brighter pictures, and had a much greater need for the cathode end to be near ground (applying high bandwidth video to the cathode or grid; the last generation of high resolution Trinitron displays delivered over 100MHz analog bandwidth!).
So, it sounds like you may have a need for the same consideration: if all your important signals are referenced to the anode, why not make the anode ground?
Of course you haven't mentioned what the cathode end is, if anything, and whether there's anything important going on down there... so you may just be screwed instead.

Tim