The one definite problem the Nexus One has, which i've noticed and others have noticed and which probably can not be fixed in this hardware revisions is the sensor placement of the home buttons, or whatever it is you call the four permanent buttons along the bottom. If you try to press in the center of where the button icon is you'll most likely miss the virtual button itself. You have to press along the top half, along the line dividing the button area from the screen, to get a consistent effect. Not only is it annoying that you have to learn to adjust your aim, but the fact that the buttons have slid up into the screen area means that when using the virtual keyboard in the normal orientation you'll accidentally hit one of the home buttons when aiming for the bottom row of the keyboard far more often than is reasonable. I'm not sure how this problem made it past QA, but i'm guessing that since it hasn't been fixed already the issue is probably with the hardware itself rather than the software. So hopefully the people to get a Nexus Two will get the benefits of any fix.
Next item. When i first got the Nexus One the screen was way too bright at the default setting. It was a lot more light than i needed and i wanted to save battery life, so i turned the brightness down a few notches. It was still brighter than i really needed, so i turned it down a few more notches. It still seemed a little brighter than i really needed, except now i was out of notches. You really ought to be able to turn the screen brightness down far enough that you can say "okay, this is definitely too dark" and then go back a step. I notice that the clock app has brightness button which lets you make the screen _really_ dark, so perhaps this is something that could be fixed in software? Unless there's something weird about AMOLEDs where below a certain brightness threshold you don't get any extra power savings.
On the other end of the spectrum, a lot of people have been complaining about visibility of the screen in sunlight. I've certainly noticed that it's hard to see anything in direct sunlight, but that's a problem that i've had with most of my electronics devices, so it doesn't really stand out as big issue to me.
I've also got some issues with button placement/sensitivity. More than once i've turned the phone off (usually for power saving reasons) and put it in my pocket, only to pull it out later and find that somewhere in the interim i've managed to hit the power button and turn it back on again. It's even more frustrating given that you can't easily double check that it's still off at a later point since there's no way to tell if the phone is really off or just in power-save mode just by looking at it. All you can do is hit the power button to see if you get either the lock screen or the boot animation.
The sound rocker button is also way too easy to hit. I prefer to keep my phone on vibrate most of the time, but i keep accidentally turning the sound off entirely or turning the volume up. I'd really like a way to disable the sound rocker, at least for notification volume, and control that entirely through a menu or widget. I actually found an app that will reset the volume back to a pre-specified level whenever it gets changed. It seems rather popular and going by the comments a lot of people have had difficulties similar to mine. It's kind of sad that we all need to download a hack through the app store in order to do something (badly) that should have been part of the OS to begin with.
I'm also not sure if about getting notifications all the time for GMail and GTalk. If i'm at my desk when i receive them then they're totally redundant and i'd rather they not be there. However when i'm not at a computer they could be theoretically useful. I wonder if someone could write an "At My Desk" app that would change certain settings based on which setting you had it on.
I like the soft case that came with the phone, it's nice and, well, soft, and it has a cute icon on it. However i have a couple issues with the shape. If i put the phone in top side up then i can easily slide it out a little bit, turn the screen on and check the time, and slide it back in. However because the top is mostly open it leaves the power button exposed to the kind of accidental activation issues i discussed above. And because it's a soft case it seems like sometimes i'm managing to hit the sound rocker through the case.
If i put the phone in upside down then the power button seems less likely to get pushed (although like with the sound rocker, it's still possible) but then i can't easily slide the phone out to check the time, and now the micro USB port is uncovered and potentially getting stuff caught in it. Also, although i haven't really used it as an mp3 player yet, that orientation would also cover up the headphone jack on the top.
I can think of two kind of cases i would like better. The first would be more or less like this, except the main hole to slide the phone in would be on the bottom. On the top would be two small holes to expose the headphone jack and the power button. Ideally having the edge of the case around but not on top of the power button would reduce the number of time it gets accidentally hit. There would also be a segment of clear plastic along the top of the case that would line up with the notification bar so you could see the time, battery power, notifications, etc without having to take the phone out of the case. The bottom would have moderately thin strap a cm or two wide which would cover the USB port when the phone was in the case. It should have snap attachment so you could secure the phone in if you wanted. A snap attachment and not velcro because i hate dealing with velcro in situation where you want to be quiet.
An even better version of the case would make the entire front of the case a flap that you could open up (again, secured with a snap, not velcro) with either a hole or a touchscreen compatible plastic cover so you could use the phone without taking it out of the case. This version would also need another cutout hole for the volume rocker (not only for adjusting the volume but for apps that use it for other purposes, like SNESoid) so it would probably make most sense for the flap to "hinge" on the right side, as counterintuitive as that might seem at first.
I've seen similar type cases for iPhones and such made of hard plastic and with no front, but i would think that the foamy stuff would offer more protection if you dropped it, and i'd definitely want some kind of protection across the screen most of the time, given that i keep my phone in the same pocket as my keys and pocket knife :)
Despite all that i'm still having lots of fun with the phone of course, and shelleycat has complained once or twice about being a phone-widow :)
Edit: Running through my ideas for the case in my head, another benefit of having the front flap "hinged" on the right side would be that when using the phone in landscape mode the connection would be along the top, which seems like the natural orientation to me in that mode, even if it is a little strange when the phone is upright.