Could have sworn I commented here already, but yes, this would certainly have it's uses. Though, in interest of flexibility, I think it would be nice if the feature could support .csv file loads in addition to Excel. I just personally prefer text files for lists of ItemRecordIDs or Barcodes, but to each their own.

In the meantime, you can TECHNICALLY accomplish this by using a SQL query to create a NEW Record Set that excludes Items in one Record Set from another. You'll need to know the RecordSetID for your two starting Record Sets, but that's easily found in the top right corner of the Record Set display in Leap. The query is also slightly different for each type of Record Set, but here's a template for Item Record Sets:

SELECT [ItemRecordID]
FROM [Polaris].[Polaris].[ItemRecordSets]
WHERE [RecordSetID] = /*Starting RecordSetID*/
AND [ItemRecordID] NOT IN (
SELECT [ItemRecordID]
FROM [Polaris].[Polaris].[ItemRecordSets]
WHERE [RecordSetID] = /*RecordSetID of Items to exclude*/
)

Again, you'll need to change the query up a little for different types of Record Sets, but it's pretty obvious stuff. Here's a template for Bibliographic Record Sets:

SELECT [BibliographicRecordID]
FROM [Polaris].[Polaris].[BibRecordSets]
WHERE [RecordSetID] = /*Starting RecordSetID*/
AND [BibliographicRecordID] NOT IN (
SELECT [BibliographicRecordID]
FROM [Polaris].[Polaris].[BibRecordSets]
WHERE [RecordSetID] = /*RecordSetID of Items to exclude*/
)

I won't bother with templates for Patron or Weeding Record Sets, but I think you get the idea. I do think this would be a useful feature to add, but hopefully this can make your workflow a little easier for now.

This would be SUCH a huge time saver. I utilize a lot of item & bib record sets for various kinds of database clean-up. If I could bulk remove from one set based on criteria it would be almost life-changing. :)

I can certainly see how this could be useful, though I'll make a plug for support for .csv uploads as well, for flexibility's sake.

I'll also mention that you can TECHNICALLY do something like this already, though it requires a little bit of SQL searching and you end up with 3 different Record Sets instead of 2. If we're talking about Item Record Sets, the SQL isn't too bad... I actually worked out the bones when I was putting all but a few hundred items at a branch that was closing for renovation into the Storage status:

SELECT [ItemRecordID]
FROM [Polaris].[Polaris].[CircItemRecords]
WHERE [ItemRecordID] IN (SELECT [ItemRecordID] FROM [ItemRecordSets] WHERE [RecordSetID] = *Original Record Set ID)
AND [ItemRecordID] NOT IN (SELECT [ItemRecordID] FROM [ItemRecordSets] WHERE [RecordSetID] = *Record Set ID of Records to Exclude/Remove)

The RecordSetID displays prominently in the top right corner of the Record Set in Leap, so you shouldn't have any trouble finding those there... In the Desktop Client, you have to open the Record Set Properties, which it a little less convenient, but still doable. If you're dealing with 10K+ entries, I expect you're probably dealing with Items, so I'll leave it at this for now... but if you'd like me to to work out a similar query for Bibs, just let me know.