This has got to be the best all-around gear combo for flats, at least for solo riding. Otoh finding cassettes that have a 16T on them is much harder than it should be. In the 9 speed world my choices are 13x23, 13x25, and 14x27. To get a reasonable, climbing-friendly 13x27 I have to get a 12x27, a 16T middle cog, and a 13T final cog. I looked at 10 speed figuring that that's the cog they've added but nope! Anyone else really like the 16T in the back but have a hard time finding the right cassette?

The most common stock 1ospd cassette is by far the shimano 12-25, which just happens to include a 16. I've got at least one spare, but, shipping from New Zealand would probably outweigh the value of such a common item. The shimano 105 CS-5700 12-27 also has a 16.

If you think that 53/16 is your most desirable gearing combination for flats, I suspect your cadence is on the low side. At a very attainable and highly desirable 95/min that would be about 25 mi/hr. Hardly all purpose. I suspect your cadence is much lower, around 70-80/min or so. Easiest solution to your problem is to increase your cadence and use a larger rear cog. Even a small increase would allow you to use the readily available 17 tooth cog.

There is no best "all 'round choice" that works for everyone, even if just on the flats. Comfortable speeds and cadence vary greatly.

Or... drop to a 50t big ring.

I agree, this is quite a big gear for riding around in solo. You should try to get your cadence up around 100 if you want to do longer rides.

I have a 6 speed cassette so my spread is huge

If we are talking about a singular gearing for cruising on the flats, 87 gear inches is on the steep side and unless you're some kind of mashing freak.

A lower gear and higher cadence is far better for endurance.

With fewer rear cogs, the solution was always to use the front shifting more to access gears on the other chain ring. We have become spoiled with 10 or 11 speed cassettes, and can stay on one front ring until the wind or the slope changes direction. But with only six cogs you may have to find something on the other ring. Instead of 53/19 for example you could use 39/14.

Okay, I'll expose my ignorance here for sure, but: I ride a standard double with a 9-speed cassette, and with the exception of the very steepest climbs (and I live in a reasonably hilly area) I don't feel the need to shift off the big ring - and I am by no means a high-performance cyclist. If I had a couple more cassette gears, I think I'd basically never need the small ring. So: with a wide enough cassette, wouldn't it simplify the drivetrain a lot to run a fixed front ring and remove the front derailleur and shifting assembly altogether? I know there's got to be a good reason why not, I just don't know what that reason is...

There was an infamous 1x10 thread about just that earlier this year. Even I sort of see the appeal of a 42-44t front and an 11-28 or so on the back for commuting and the like. The thing is, front derailleurs are cheap, light, and give you more flexibility, especially since with a 1x10 or 1x11 you'll probably want a chain keeper of some sort. Having the FD also allows your cassette to be tighter, which gives cleaner shifting and better control over cadence.

I ran my commuter for a year that way, with an 11-30 cassette so I say yes, it has all the advantages you suggest. Sheds some weight too.

"commuter" is relevant: I had all the gears I wanted for that particular route. On more varied terrain or with a group some higher and lower gears are handy. The other disadvantage being the larger differences between gears which is difficult for those who like to keep a particular cadence going. Like OP for instance.

53-19 is my common flatland gear. Allows me to spin up from 80 to 95 rpm pretty easily. Cruise at 75-85 spin up to 95 on a straight or slight rise. I'm currently at 150 watts steady state max so the gear allows me to push above upper limit..say on a 3 minutes interval where I push hard as I can on hoods and roll (solo) 21-22...occasionally a bit higher but i can't spin (easily) much faster than 105. Any faster speed takes the drops. My long term goal is to get to 200 watts steady state output and that likely means 18 or 17 on the rear unless I roll at 90 rpm all the time (possible). I now have real appreciation for the TT and Tri riders.

Great point. I have a 42 small ring. I really should be using it a lot more
Feels like I'm spinning faster than I'd like in the middle of my cassette when using the 42 and don't wanna crosschain it too much
Of course when the hills come, it's perfect (although a 39 small ring would be so much better)

My touring bike trips the scales at 37 lbs. I have a 52-42-30 triple crankset, and I basically use the middle ring (42) 95% of the time. I think it is quite feasible to go to an 1x11 combo that has a 42-44 chainring and an 11-34 cassette.

I got a 50-39-30, 12-30 10 speed, and 39x14 is quite usable on flats. Bumping the mid ring up to 42 shouldn't change too much.

I get almost the same ratio with a 50/15, and quite a few different 7-speed cassettes have that. Life is good.