So, assume you're flying from a Canadian airport without US pre-clearance (YQR if reality helps you).
Assume you want to fly to DCA/IAD/BWI. Assume you're a nervous flyer whose calm flyer husband is flying a day before to New Brunswick before heading to DCA, so you'll be doing this yourself. (Assume you're slightly grumpy that your husband is going to Fredericton first but he sees it as an opportunity to make some people happy, plus get two extra flight segments and a bunch of status miles. )
Where would you want to clear US Customs? (We're looking for the calmest experience here.)
The flyer in question (my wife) has NEXUS and Global Entry so that helps immensely.
The airports through which she can fly and do US Customs are YYZ, YOW, YUL, DEN, MSP and ORD. She's recently flown through ORD (three weeks ago) and knows how to navigate it, and has flown through DEN a couple of times but not cleared Customs there for a couple of years, before they had GE. (MSP and DEN both have GE now, or will in the next few days. ORD has had it for a few years.) She's not cleared US Customs in YYZ since 2003 so everything has changed, and I fear the gong show reputation will make it a bit hairy. (Might it be best if she just exited the terminal instead of going to connections, then entered US preclearance as if she was originating at YYZ so that she can use NEXUS? I don't think there is NEXUS via connections.)
Sorry to be so rambling, but I hope you get the gist of what I mean.
A couple of the flights involve tight connections (~75-90 minutes) but even with NEXUS/GE, I'm thinking that at some airports that's just too tight.
Location: Home:HKG/YYZ Business:YVR, LAX, SFO, SEA, PVG, PEK, CAN, NRT, MNL, SIN, BKK, KUL
Programs: DL girl's best friend, Lifetime(DL's) SC, IC RA, SPG, AARP, Nexus/GE, APEC(HK)
YYZ has NEXUS at CBP preclear checkpoint. It is the only way to access US departure area.
A domestic arrival one would enter the terminal and head over to US departure. I do not believe there is any distinction between connecting to US passengers and local departing US passengers. It is the same lineup.
Timing of connection: it depends on time of day and day of the week at YYZ. If she is not adverse to waiting in the US departure area I would allow for more time. Monday morning and Thurs/Friday afternoons are notorious US bound rush hour as far as YYZ is concern.
The lowest tension way is to clear immigration and customs in the US at the end of your last flight - the added delay won't affect your getting on a flight. Porter's flights to Newark and Chicago out of YTZ are examples. A side benefit is that you are getting onto the flight into the US without an agricultural inspection, which means you can bring your own lunch. Nexus isn't used at the US airports, Global Entry is - it is a free addition to Nexus membership.
Unfortunately, doing it at the destination won't be possible although I agree with you that it's best. DCA doesn't even have US Customs, and YQR will never have a non-stop there due to being outside its perimeter.
I also can't see YQR-IAD taking off anytime soon.
I've come to favour xxx-ORD/DEN-YQR trips from the US of late, though, for that very reason. Get to YQR, clear Customs, go home. Very convenient.