This may not be conclusive testing to suit all your end purposes, but I wanted to report back here that I ran a simple test today on the index layer of one of my existing DDP mxds and I was able to set the definitionQuery property and successfully refresh the DDP so that other operations such as exporting, printing, etc., recognized the 'new' index (no adding, removing, or updating the index layer was necessary). I imagine you've got enough other layer updates to do than to worry about where your index layer reference went (remember an earlier post I suggested creating a 'master' fc containing all county grids so that you can filter them by county from the layer object perspective using a def query).Here's an abbreviated example:
import arcpy
arcpy.env.workspace = r'< your workspace string (mine was a gdb) >'
testdoc = r'< your mxd path >'
mxd = arcpy.mapping.MapDocument(testdoc)
df = arcpy.mapping.ListDataFrames(mxd, '< your dataframe where your DDP index resides >')[0]
# set layer object reference to the index page
lyr = arcpy.mapping.ListLayers(mxd, '< your index layer name >', df)[0]
# create the appropriate field delimiters for the query string based on the workspace type
indexPageField = arcpy.AddFieldDelimiters(arcpy.env.workspace, '< your index layer page fieldname >')
# create the query, in this case, filtering for pages less than 6 (pgs 1-5)
qry = indexPageField + ' < 6'
# set the layer objects definition query
lyr.definitionQuery = qry
# finally, refresh the DDP -- this is the critical step which will crash if the query is unacceptable...
mxd.dataDrivenPages.refresh()
# here you can test the DDP by getting the pageCount, printing, exporting, etc...
pgCnt = mxd.dataDrivenPages.pageCount
print pgCnt # based on the query, results in 5 pages
# success!
# try changing the definition query to see if the DDP changes correspondingly
qry = indexPageField + ' < 11'
lyr.definitionQuery = qry
mxd.dataDrivenPages.refresh()
pgCnt = mxd.dataDrivenPages.pageCount
print pgCnt # based on the changed query, results in 10 pages