This is a very long ongoing debate. There are the mathematicians out there that will insist there can be no difference, I am of the camp that I understand there can always be a difference, so I spent a long time ripping many files, all in DB Poweramp, using a very highly resolving system including an Esoteric D-70 (PCM 1704 DACs), RME 9632 Sound card, ASIO, custom made $800 digital output from RME soundcard into my DAC via XLR. All running direct into my Pass Labs amp using the DAC as a volume.
Now maybe there are differences with USB? I have found USB to be vastly inferior to SPDIF or XLR or even Toslinnk for that matter.
With that being said I found HUGE differences between playback software and settled on JRiver.
Back to WAV vs. FLAC, I would have willingly ripped all to WAV but again found zero difference, I wish I could have but couldn't.