In almost all cases de-duplication should be left enabled. Veeam uses source side de-duplication which will decrease the amount of data that must be transferred to the target repository. This is true even when used with hardware de-duplication appliances as well as during replication which will reduce the amount of data being replicated.
For very high change rate VMs such as Exchange and SQL servers, there can be significant advantages to choosing WAN target mode (256K block size) even for local backups. However, there is a cost to pay in CPU overhead when choosing WAN target mode. Testing in the field has shown a reduction of 50% or more in the size of incremental data when using WAN target mode for incremental backups of highly transactional servers.
For compression, the Optimal level is almost always the best, but if the target is a hardware deduplication appliance, you will generally achieve the best compression and deduplication ratios by writing the data to the storage uncompressed, or by using Dedupe-friendly compression level. Since the repository has the option to un-compress the data prior to writing it to the target, this option is the recommended one for such cases.
There is also an option to align the data on 4K blocks, which can be helpful for dedupe storage that uses fixed block sizes.