GeoData.gov — A collection of GIS data from many federal agencies.
NationalAtlas.gov — National data layers from various different agencies.
Census.gov — The Census bureau does double duty mapping the US in order to be able to take an accurate census. They provide all of their data as public domain.
BTS NTAD 2007 — Bureau of Transportation Statistics National Transportation Atlas Database for 2007
California CaSIL — A collection of layers about California; mostly focused on politics and ecology.
San Francisco City and County
San Francisco SFGIS — Mostly focused on infrastructure. Requires signup, but free.
Sedgwick County GIS — A collection of layers about Sedgwick County and the Wichita area; mostly focused on infrastructure and cartographic features.
Massachusetts MassGIS — Lots of high resolution data; mostly focused on infrastructure.
Nevada Bureau of Land Management — Lots of great layers; mostly focused on BLM events such as fires, cartographic features, and land management data such as herd areas.
Washoe County Data Warehouse — Lots of freely downloadable useful layers; mostly focused on geographic and cartographic features.
City of Reno GIS MapServer — MapServer doesn’t work in Firefox, but you can request data layers for download (by fax); data available is really focused on planning and city zoning issues.