There appear to be two USGS topo map sources available, US Topo (CalTopo, USGS) and ESRI USGS Topo.
CalTopo has high resolution scans, so the test and lines remain very clear when you zoom in. But when you zoom out, color matching of the scans is pretty bad -- you see a patchwork of different shades of the same color. That's ugly, but not a usability issue. The real problem I have with CalTopo is that as you zoom out it doesn't switch to smaller scale maps. You are looking at the same 7.5' topo maps zoomed way out, so you can't read anything at all or tell where you are.
ESRI has the identical topo maps, but in shaded relief. I don't like shaded relief, but it's not a serious usability issue. But a big advantage of the ESRI maps is that, as you zoom out, it switches to different scale maps, so there is never a problem reading the maps at any scale. It would be nice, if at the smaller scale, it would show political boundaries and roads, instead of just a shaded-relief map of the U.S., but for the most part it's much more easy to navigate these maps when zoomed out. The biggest annoyance of the ESRI maps are that they are scanned at lower resolution than the CalTopo maps. You can still read everything, but things get blurry and JPEG scanning artifacts become evident at high zoom levels.
It sure would be nice if the good aspects of CalTopo (high resolution scans) could be combined with the different map scales of ESRI. Is there any hope for such a thing?