Gah, I finally solved it. I hope this helps someone else out.
It came down to the "other software" that our stuff relies on, in this case, ArcGIS Server. The uninstall/reinstall of it somehow managed to leave duplicate entries on multiple paths in the applicationHost.config file for IIS.
There were four entries:
<add name="ESRI_mapHandler" path="ESRI.ArcGIS.ADF.Web.UI.WebControls.MapHandler.ashx" verb="*" type="ESRI.ArcGIS.ADF.Web.UI.WebControls.MapHandler, ESRI.ArcGIS.ADF.Web.UI.WebControls, Version=9.3.1.3000, Culture=neutral, PublicKeyToken=8fc3cc631e44ad86" preCondition="integratedMode" />
<add name="ESRI_tileHandler" path="ESRI.ArcGIS.ADF.Web.DataSources.ArcGISServer.TileHandler.ashx" verb="*" type="ESRI.ArcGIS.ADF.Web.DataSources.ArcGISServer.TileHandler, ESRI.ArcGIS.ADF.Web.DataSources.ArcGISServer, Version=9.3.1.3000, Culture=neutral, PublicKeyToken=8fc3cc631e44ad86" preCondition="integratedMode" />
<add name="ESRI_mime" path="ESRI.ArcGIS.ADF.Web.MimeImage.ashx" verb="*" type="ESRI.ArcGIS.ADF.Web.ImageHandler, ESRI.ArcGIS.ADF.Web, Version=9.3.1.3000, Culture=neutral, PublicKeyToken=8fc3cc631e44ad86" preCondition="integratedMode" />
<add name="ESRI_mime91" path="ESRI.Web.Controls.MIMEImage.aspx" verb="*" type="ESRI.ArcGIS.Server.WebControls.ImageHandler, ESRI.ArcGIS.Server.WebControls, Version=9.3.1.3000, Culture=neutral, PublicKeyToken=8fc3cc631e44ad86" preCondition="integratedMode" />
These entries were duplicated in the
<location path="Default Web Site">
<system.webServer>
<handlers>
and the
<location path="" overrideMode="Allow">
<system.webServer>
<handlers accessPolicy="Read, Script">
paths of the config file. Removing the four entries under the Default Web Site path solved multiple issues!
I guess IIS was attempting a metabase write, but because the config file was bad, it just wasn't happening in certain cases.