This is a userscript, but when it's installed it inserts a menu item called Blacklist on AO3's nav bar. Clicking that opens a box on the page, which is where you customize it.

• This is a global blacklist, but since it's right there it's pretty easy to change on the fly.
  
• The box has basic instructions on it to let you know what you can do.
  
• This needs specific terms.
  
  • If you want to blacklist all AUs, put alternate universe* in the list, using the * as a wildcard to cover everything. If you want to blacklist all vampire AUs, put alternate universe - vampire into the box.
    
  • If you have an OTP and really, truly don't want to see anything that includes either member of that pairing in a paired relationship with someone else, you can use first character&!second character