What are the differences between these two mail preferences within iCloud settings?
The first option, System Preferences &rarr; iCloud &rarr; Mail, controls whether the iCloud Mail account is available in the Mail app. Unchecking this option will remove the account from Mail, along with all the associated email. This won’t permanently delete the mail: it will still be accessible on iCloud.com, and in Mail if you switch the option back on.

The second option, System Preferences &rarr; iCloud &rarr; iCloud Drive Options &rarr; Mail, controls whether Mail can use iCloud Drive. This is used when you try to send a file that is too large for email; you will be prompted to use Mail Drop, where the attachment is uploaded to iCloud Drive and transferred senselessly to the recipient.