Tons of file_usage queries
As it turns out, in the system_cron was ultimately causing the query storm. The particular bit of offending code was:

$result = db_query('SELECT fid FROM {file_managed} WHERE status &lt;&gt; :permanent AND timestamp &lt; :timestamp', array(
    ':permanent' =&gt; FILE_STATUS_PERMANENT,
    ':timestamp' =&gt; REQUEST_TIME - DRUPAL_MAXIMUM_TEMP_FILE_AGE,
  ));
  foreach ($result as $row) {
    if ($file = file_load($row-&gt;fid)) {


As it turns out, there were about 200k files which matched that first query. It would then loop through them all and check to see if they had any references remaining. Since it had to do this check that may times, it was hammering the database and causing a decent amount of slowdowns. Additionally, it wouldn't find anything to prune since all of those files are still presently in use.

The solution in my case was to simply set the status field to 1 on all of the offending records, since they weren't going to change any time soon (these are product images whcih don't get updated often). The full consequences of that are unknown to me, but it seemed like a reasonable fix.