Not if this case is anything to go by. The site had already been blocked in Hong Kong, India, Saudia Arabia, the United Arab Emirates and Malaysia; so it wasn't just the US Government going after the site - and in this particular case also had the cooperation of authorities in Hong Kong and New Zealand.

Added onto which, the case rests on existing law - and not just the DMCA.

The indictment concluded that Megaupload differed from other online file storage businesses. It suggested a number of design points of its operating model as being evidence of criminal intent and venture: In practice, the "vast majority" of users do not have any significant long term private storage capability. Continued storage is dependent upon regular downloads of the file occurring. Files not downloaded are rapidly removed in most cases, whereas popular downloaded files are retained.   Because a small proportion of users pay for storage, the business is dependent upon advertising. Adverts are primarily viewed when files are downloaded and the business model is therefore not based upon storage but upon maximising downloads.   Persons indicted have "instructed individual users how to locate links to infringing content on the Mega Sites ... [and] ... have also shared with each other comments from Mega Site users demonstrating that they have used or are attempting to use the Mega Sites to get infringing copies of copyrighted content."   Persons indicted, unlike the public, are not reliant upon links to stored files, but can search the internal database directly. It is claimed they have "searched the internal database for their associates and themselves so that they may directly access copyright-infringing content".   A comprehensive takedown method is in use to identify child pornography, but not deployed to remove infringing content. (item 24)   Infringing users did not have their accounts terminated, and the defendants "made no significant effort to identify users who were using the Mega Sites or services to infringe copyrights, to prevent the uploading of infringing copies of copyrighted materials, or to identify infringing copies of copyrighted works" (item 55–56)   An incentivising program was adopted encouraging the upload of "popular" files in return for payments to successful uploaders. (item 69e et al)   Defendants explicitly discussed evasion and infringement issues (69i-l) Source: Wikipedia

Note also that similar services such as RapidShare and MediaFire haven't been targeted, and RapidShare has convinced a German court that only a minority of the files it hosts are illegal, and that it swiftly complies with takedown requests.