My personal mantra is: never try to use software to do a job that hardware can do. Hardware is (in general) much more robust and adept at doing certain things. Take advantage of that and let the strengths of software (it's visual, effects are usually easier to apply, editing is generally easier) do what software is good at.
I think the hardware vs. software decision depends on what you're doing. To be honest, I wouldn't ever want to go back to using my R16 in standalone mode for recording, but then I generally don't just set everything up to record sets. I usually do tracks one at a time and it's so
much easier to do that in audio interface mode with a laptop at my side.
For example, I recently did a session with a vocalist laying down several tracks of lead and backing vocals. For the leads he did each verse individually and then came back and did all of the choruses. Then he laid down the backing vocals by laying down all of the similar parts one at a time. The constant skipping around was dead easy on the PC; the thought of doing it with markers in standalone mode (especially since inserting a marker renumbers everything after that - UGH!) makes me cringe. That session literally took less than half the time it would have in standalone mode, plus I was able to tweak things on the fly instead of waiting until I copied from the SD card to a computer afterwards.
And don't get me started about punching in with standalone mode versus interface mode - painful in standalone mode (including more of the above-mentioned hassles with marker renumbering) and just a few seconds of effort in interface mode.
Different strokes for different folks, and for different recording needs. I wouldn't dismiss interface mode too quickly. Yes, it can take a bit of work to get there (although I just plugged everything in, brought up Reaper, and it all just worked), but once you have it set up you're good forever, and the time savings will definitely pay off many times over as time goes by.
As always, just
from some guy on the innerwebs.