It is recommended to upload known unsubscribes and hard bounces into a new instance when configuring Eloqua. By doing so, you can have a clean start in the new instance and accurately manage the communication preferences of your contacts. Additionally, it is important to configure a separate program to handle known unsubscribes and hard bounces to ensure compliance with privacy regulations and prevent sending unwanted emails to contacts who have opted out or whose email addresses are no longer valid.