One point brought up by sipa here in a semi-related thread ([WIP] p2p: Add random txn's from mempool to GETBLOCKTXN by davidgumberg · Pull Request #27086 · bitcoin/bitcoin · GitHub) is that the number of TCP packets sent over could increase if we’re making the CMPCTBLOCK message larger with prefilledtxns. I think that is maybe one downside to prefilling transactions. Perhaps it’s possible to prefill transactions up to a certain total message size limit specifically for compact blocks?
EDIT: His point was actually about the GETBLOCKTXN causing more round trips, but the same thing applies.