NA VE tuning...
You could slap on a VE (NOT DE!!! - you'll see why I'm pissed about this when I link up my Mods II page) header 4-5hp, K&N cone 1hp, properly tune the ECU 3hp, pulleys 3-5hp, overbore 1mm 5hp (or go the JUN route and re-sleeve to 2-4mm 10-15hp), ex-hone the intake manifold (some say you need turbulence here but I look at the STR in the Honda camp and think there is potential here) 2-5hp.
Don't bother with compression, its already 11:1. The crank is already lightened but you could balance everything.
The aftermarket will NEVER make some of this stuff so it will have to be a one-off.
>how much room is left for improvement on the VE?
Not much
>Is the high-rev cam on the VE way way more efficient than the S-3s?
No, I don't think so. The VE's extra hp is about half in the lobe-switch and half in the higher compression and exhaust/intake manifold optimizations. People expect too much from this motor. Don't get me wrong, I love the damn thing.
>Will there be a point soon where these new I4s are SO efficient in stock form that tuning is going to be much less cost-effective?
Has tuning ever been cost effective?

I know what you mean, but speed has always been a quesion of money. How fast do you want to go?
Look at the Skunk V-Tech Integra. The high-power NA route is for very smart and dedicated people with resources for R&D. This is why I went turbo.