Well he's talking about a UART chip so I'd say that's relevant.
That SC16IS752 is a nice-looking chip, I'm currently working it into a design.
I plan to use an MEGA because it as a lot of I/O.
True, but you need UARTs not GPIO and it only has 4.
Now while Software serial cannot rub it's tummy and chew gum at the same time it may work IF the commands are staggered. IE if you can control the timing of the commands you could read 1, write 1, read 2, write 2 etc etc.
If the command timing is random/asynchronous then you have to use more UARTs and the SC16IS752 has 64-byte FIFOs so if your commands are < 64 bytes you don't even need to use RAM for buffers.
In both cases I see little benefit in using a Mega although the extra RAM may be useful for buffers if you can use SoftwareSerial.
Rob