Of the ones in existence now, I'd rate those built on ITA engines like NW as the best and others like United as the worst (excluding sites of carriers outside the U.S., which can be dreadful).

Supporting all the partnerships and partner flights is something I'm sure a lot of people would like to see. ITA might show NW itineraries priced out with DL or CO flights, but your odds of getting those called up on the NWA.com site are slim, especially for complex itinararies. And chances are if you plunk it in segment by segment you won't get the price, even if you can get all the segments to come up.

Partner segments on award travel are another thing. NW probably has the one of the best online bookings (with a limited but still rare multi-city capability), but the call centers still get the $15 calls when people try to add CO or DL to the mix in hopes of getting something to work.

It'd also seem that supporting STOPOVERS better would be needed if the big carriers would ever stop treating those and one-ways like the work of the devil. Some will use stopovers (usually poorly) as a marketing tool, like UA for DEN or HP for LAS. But website support isn't good.

One big thing the OP has going for him is that many people notice the booking shortcomings of websites when the alternative is to try to deal with one of those infurating voice systems or pay $15 to book through an agent. Hopefully that'll drive improvements.