yes, there is a difference (that is if you are actually using a real i2s output board on the Oppo). I2S is the native PCM bit information for each channel. There are two separate channels that require two different connection.
S/PDIF will take the 2 channels of i2s data and encode it all into a single bitstream. It is clocked the same, but transmitted over a single wire. At the receiving end, the device has to decode the bitstream and separate the data out into two i2s channels again. This raw i2s data is what is sent to the DAC chip.
If you use the standard HDMI video output of the Oppo, you need to connect this to an A/V pre/pro or receiver. The Oppo will take the S/PDIF data and break it into HDMI data packets (essentiall de-clocking the S/PDIF signal because the data packets are merged into the HDMI audio/video data using HDMI clock signals). This is what is called PCM-over-HDMI. The pre/pro or receiver will have to extract the audio data packets and re-clock that into the proper PCM sampling rate before sending it to the DAC.
If you compare PCM-over-HDMI with a normal S/PDIF coax connection, the S/PDIF coax will generally be superior and have much more dynamic range and better sound.