The headspace will much more easily lead to oxidation (staling) of the beer as it sits in the keg. If you are thorough about purging as noted above, you can mitigate that. But it certainly wastes CO2 to do so.
I also evolved to brew 2.5 gallon batches, and a while back I just caved and bought a few 2.5 gallon kegs, price be damned. It was the right product for my needs, and worth the brief moment of cognitive dissonance when making the purchase.
Now, you can actually ferment and serve from the same 5 gallon kegs if you use a floating dip tube like the Clear Beer Draught System or the similar product from William's Brewing. I am now doing this all the time, actually, and it's great.