Every Thingworx entity has a service for adding tags and removing tags. You simply pass in the tag that you want to add or remove. For example: http://server/Thingworx/Users/ryan.miller@thingworx.com/Services/RemoveTags?tags=Applications:FancyApp will remove the 'Applications:FancyApp' from the User ryan.miller@thingworx.com.
Assuming that you are referring to ThingWorx scripting, in the current 3.2 version you cannot 'directly' script to a Mashup. In theory you will be able to do the following in 4.0:
var params = {
tags: undefined /* TAGS */
};
Mashups["<MashupName>"].RemoveTags(params);
...but as Ryan points out you could always use direct API calls in external scripts...this could even be facilitated in a ThingWorx script using the ContentLoader Resource Post functionality, although we don't consider it best practice to call a ThingWorx API (via URL) from within a ThingWorx script.
