The biggest are that not all filtering capabilities are supported in MV3 and that the filter lists are only updated when the extension itself is updated. More details in the uBOL FAQ:
I know Safari can be fast, but is it up to scratch in terms of security? I remember reading somewhere that it doesn’t even isolate tabs as separate processes.
That hasn't been true in like 10 years. You can check the process hierarchy yourself in Activity Monitor and see its many processes, including one for each loaded site. It also uses separate processes for sandbox access, image decoding, video decoding, Metal compilation, and audio, among others.
