[Lonman]

You would have a lot better sound & a much easier time with an external crossover feeding both the subs & mains - only because you are not crossing over the tops at the same frequency the subs are so they are trying to reproduce the sub frequencies still as well running into some possible phase cancellation & loss of frequencies in some of the low end. A crossover point of 75-100 is more ideal for subs as well.
That being said, the XLR & 1/4" balanced main outputs can be used simultaneously giving you main volume control for both amps you wish to push. It will be better than using a tape out for a connection.
The computer hooks to the mixer via a USB cable only, no need for the 1/8" mini jack or anything else. The PROFX actually acts as a I/O sound interface so could be used on a computer with no sound card at all - the mixer IS the sound card!

1/4" balanced is a tip/ring/sleeve - looks like a standard headphone plug. An unbalanced is a tip/ring - looks like a 1/4" plug you'd plug into say a guitar.
I attached pics of a bal & unbal plug - notice the extra ring on the balanced plug. For the Mackie output, use the balanced on the mixer & if your amp has XLR inputs, go balanced 1/4" - to XLR (determine whether you need male or female on the amp).
You could try to run both programs at the same time, but like said they may try to cancel each other out - even if only one is sending a signal.