Only if the reason of defederation does not actually warrant a defederation. If mastodon.social suddenly promoted nazi content or whatever there would be no doubt that it needs to be defederated no matter how big it is. (Look at pawoo.net, which has apparently over 800.000 members). Defederation (esp. collectively via fediblock etc) is a nuclear option that shouldn't be used for petty reasons. It has huge implications for those instances.. basically death.