If your question is optical vs HDMI, I'd say you'll have to experiment.
Both are passing a digital signal.
I have two surround systems set up here and use my receivers for all my audio/video switching via HDMI. Nothing is connected via optical any longer that has the capability of HDMI.
I have my satellite receivers, a PS3 - aside from games it is used for Netflix, Vudu...; 2 HD-DVD players; Blu-Ray player; a Win 7 HTPC which is used for iTunes, Amazon's Unbox video, hulu, cinemax, netflix... the list goes on; a Roku player...
All are connected via HDMI for audio and video. I have not done any comparison of the audio from the same device trying optical vs HDMI, but I would venture there would be no difference.
I did experiment comparing my MBP via optical and the HTPC via HDMI and I could discern no difference between the two of them on an Onkyo/Infiniti set up listening to music I am very familiar with.
It's also going to depend on the specific Denon you have and the quality of the individual electronics of the optical vs HDMI.
My guess would be, that if you can hear a difference, you'd have to be listening so hard to tell the difference that it would spoil your enjoyment. I don't think the difference would be to the point where you could hear things on one input that you couldn't hear on the other... or have a better frequency response on one vs the other.
The last time I looked at Denon in a serious way was pre-HD audio and ended up going with Yamaha instead. I don't know that you can even set up an HDMI port and assign an optical input to it for the audio portion.