Need Guidance on Optimizing Complex Vector Artwork for Performance in Adobe Illustrator

@johnson_7706 here's my two-cents workflow in green:

Best practices for handling large, intricate vector compositions in Illustrator

• Any recommended workflow for separating artwork into manageable sections?
  Are you saving the final Illustrator files as PDFs? If so, save the files as PDFs (but make sure you keep and save Illustator AI file with version control (version 1, version 2, etc); By saving the smaller PDFs in chunks, you can use Acrobat Pro to combine them into one file
  
  

• Tips for structuring layers and groups to reduce overhead?
  I would link my images not embeded because if there are any changes, it would automatically update for me but also it will keep the AI files down smaller as well. 
  
  

Optimizing gradients and meshes

• Are there known performance limits for gradient meshes or blend steps?
  I rarely use gradient meshes and blend steps. If I had too, I make rasterized the vector file when I am done with the gradient meshes and blend steps to 300ppi
  
  
• Ways to simplify them without noticeably affecting visual quality?
  As above. 
  
  

Exporting heavy artwork

• Suggestions for fast and clean export settings for digital and print?
  If you are saving for the web, you can use the 'Save for the web' feature as a PNG (which is a lossless format, no data is loss if you have to re-save the image). I would also save the image as  PNG24 because it has 16.7 million of colors compared to PNG8 but the file size is bigger. But, I also would use tinypng.com, a third party website to strip out any metadata, and color profiles but it does keep it's quality but the file size does go down a lot! 
  
  For print, I would combined the PDFs into one and save a combined PDF at the highest quality setting unless you have the commercial printers profile settings. For that matter, you can even save a 'smallest file size' for the web 
  
  
• Should I flatten certain effects before exporting?
  Yes, for me if I am using gradient meshes or lots of blend steps or anything that may be an issue 
  
  

Hardware considerations

• Does Illustrator benefit more from CPU cores, RAM, or GPU for this kind of work?
  I use an older MacBook Pro with 16gigs of RAM, and I have no issues with Illustrator; some of my students have had 8 gigs of RAM, and they suffer big-time; WIth AI, a bare minimum is 16 gigs and and as much as you can afford (I want to get a newer MacBook Pro with at least 96gigs of RAM because AI will likely need it one day!). The graphics card with a more powerful GPU chip will definetly will go a long way too! 
  
  
• Any specific optimization settings you recommend?
  I tell my students that I have '0' recent files to show, the least amount of undos and fonts showing. But for them who are starting out this could slow down the speed too. I let them to decide if they want to be like me or not. If I am running with large files, I make sure I close off applications, nothing streaming in the background (music or videos); close of any open tabs not in use. Each web tab open takes RAM! If it means I only have Illustrator opened, so be it! For that matter, resetting the preferences in Illustrator can absolutely help with general sluggishness, mysterious bugs, and performance problems.
  
  

Not sure if that helps, this is one person's workflow, and it may not be the same with the next person. Good Luck!