It's simple - lots of equipment outputs S/PDIF like CD/DVD players, etc, but only computers output USB. Most DACs use USB to S/PDIF or USB to I2S converters and feed the converted digital signal (S/PDIF or I2S) to the DAC chip; that means that the USB input module is just an extra part to the same DAC unit which costs more money than the DAC without that module.
As for audible differences between the two, this isn't exactly as simple - it depends on the quality of the output of the source and input of the DAC.
1) The output signal has to be strong, bit-perfect, low noise, low-jitter and precisely clocked. If both S/PDIF and USB meet those requirements, they should be the same, but since there are very few (if any) "high quality" USB units on computers and lots of dedicated sound-cards that are meant to output as close to perfect S/PDIF, it's more likely you'll get a better S/PDIF signal than USB. Both protocols are streamed and without any error correction so if the signal is off in timing or gets corrupted in any way, there is no way to change it, that is what the DAC will receive.
2) The input receivers must be of good quality, resistant to noise and be run off clean power supplies. Obviously quality here matters - if the USB receiver is REALLY good and the S/PDIF receiver is not, you'll have a better USB signal. How the DAC works also matters: if you have a DAC that runs off S/PDIF signal, than using USB is another link in the chain (USB-S/PDIF converter), so it is more likely you'll have a better signal off S/PDIF. If though the DAC is fed I2S in which case both S/PDIF and USB are converted to I2S, the quality of the receiver is the only thing that should make a difference.
Hope that helps, mostly background info, you make up your own mind as which route to take and hopefully research the DAC you're looking at to see how to best connect it.