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If PC stands for desktop, I’d go through a line isolator in any case, since stationary computers are likely to be earth grounded and will produce a ground loop with other gear (if not already with the mixer). Portable units are normally isolated and should work either way.
Option 1 is obviously worst, not only because of the non-symmetric connection, but also since most integrated sound chips are not well enough designed to produce a clean signal at all. If the output itself is clean enough (to get amplified without noise in order to be sent to a PA), a line isolator with symmetric connection to the Qu (not ST3!) may work very well though.
If the integrated sound chip isn’t clean enough, an external audio interface along with line isolator may be fine (Option 3). This must not necessary be USB, many modern PC/Mac have an optical S/PDIF output as well, so a simple S/PDIF to Audio interface will do and you’ll get line isolation for free.
For Option 2 you should be aware that even if you only need two channels, the USB-B connection will always be a multichannel audio interface and require a decent quantity of system performance to run reliably. And it may be difficult to send your audio to the correct pair of channels, if your applications are not multi-channel aware.
You’ve missed Option 4 to use AirPlay… 😉