Frame geometry, reach, drop, bar bends, placement of brakes/hoods. All of it adds up.
I'm 5'11", with somewhat longer than average arms and thighs. I'm comfortable with 56-60cm frames, with the usual adjustments to suit the bike.
I'm most comfortable standing as erect as possible for out-of-saddle pedaling, and feel best on my Univega Via Carisma (58cm or 60cm, I'm not sure how Univega measured their frames). I'm on my third set of handlebars in three years, going from flat and riser bars with upward-angled stem slightly above saddle height; to horizontal/zero-angle stem and albatross bars at saddle height. It feels natural. And this bike and albatross bar are fairly noodly, with a longer wheelbase than my road bikes. I vary my hand position from the grips to the forward arc of the albatross bar, with only a small adjustment in my body position to maintain good balance.
I have a 58cm Centurion Ironman with typical period aero brake hoods. It's set up pretty close to 1960s-'70s racing style, stretched out with less drop between bar and saddle compared with the trend of the past decade. After lots of experimenting I've settled on the conventional drop bar with the drops tipped slightly down so my wrists are straight. I've moved the hoods up about an inch. And I've switched from a 120mm (or longer) stem to 90mm to reduce reach and neck strain. Much better than the original factory setup, which felt unbalanced when standing to pedal. Too much weight forward rather than going into using body weight to stomp the pedals. My compromise adjustment works better for standing.
And I have a '93 Trek 5900, 56cm. With the aero brakes/hoods and drops comparable to a compact version of my Ironman's drops, the bike felt slightly unbalanced compared with the Ironman, but that's because of the Trek's original Ibis titanium stem, which is very long for me, around 130-140mm. After a few rides I adapted, but wasn't as comfortable as standing to pedal on my Ironman (and neither road bike feels as well balanced and efficient as the Univega for standing).
About a month ago I switched the Trek 5900 to MicroShift brifters, which are comfortable but much longer than the 1980s Suntour GPX and Shimano 600 brake hoods. So it took another few rides to adapt to the new, lower, forward balance while standing.
The road bikes don't look radically different in setups, but the balance feels very different.
In actual practice, my typical speed on the same familiar climbs is about the same with all three bikes, when standing to stomp uphill. But they feel very different. My quads start burning sooner with the road bikes, especially the Trek. Just a bunch of small differences that are significant when added up.
My solution for now has been to adjust my body position to suit the bikes. I lock my elbows on the Trek 5900 to get as upright as possible to shift more weight back. It's less aero but feels more efficient.
Based on these experiences, if we had significant climbs here (we don't, it's mostly rollers with lots of short, steep sprint-climbs), I'd probably prefer a slightly large (for me) frame, 58-60cm, to keep the bar top almost level with the saddle, and a shorter stem for a comfortable reach. It wouldn't be as aero for downhills and flat terrain. But it would suit me better for climbing.
But a 54-56cm frame with lower bar and appropriate stem length would accomplish pretty close to the same thing.
Reminds me, I need to video myself on the road bikes to check fit. I've done that before and it helped with bike fit issues.