At least it is a pile of Excel and not a pile of something else 🙂
Just an idea: use a File Geodatabase to as the data container for all of this data management processing you wish to do. I've simply resigned to the fact that the system engineers at ESRI have tightly coupled the GDB to ArcGIS for a reason and therefore perhaps it is a good idea to follow. That is, I've found that moving to the gdb model (for example, moving my attribute tables into this container) a good chunck of my problems simply go away.
I say it may be worth the effort to skip this idea of tightly coupling your GIS processing to Excel as it can be a management nightmare (field mapping, nulls, field naming, changes to the base excel tables, $Sheet management, blah, blah, blah) just is downright unappealing IMO.
I'd look into making my first Python effort that of converting the Excel tables to a FGDB (it can hold 2 TB from last I heard). All of your joins and such will be on their best behavior then and you will have a lot more control over that source data.
Does that make sense?
I'd like to hear other suggestions, but personally this would be my first move.
Edit: just to add to my post. I'd also consider doing all of your joins and follow-up exports within the "IN_MEMORY" workspace if possible. You will gain peformance and can easily cleanup the residual data left behind, while generating your desired output to disk.