Todd,
Down firing does restrict air flow (like having a port too close to the wall but even more so), so that would have to be taken into consideration in the design, including the length of the spikes (some even add a solid platform underneath to ensure the right distance and material is underneath).
Having the amp in a separate cabinet does help avoid microphonic vibrations, but frankly this is a rather minor consideration for amps designed for such service as evidenced by all the active subwoofers and professional speakers in the world.
Regarding concerns over length of speaker wire, just follow general guidelines (8 ohm load = 16 gauge 20ft, 14 gauge 35 ft, 12 gauge 60 ft and half those lengths for 4 ohm loads).