Asking "Seriously?" is similar to asking "Really?" There's a bit of a difference between them, though. You ask "Really?" when you're surprised by something. When you ask "Seriously?" it often means that you're surprised, but also annoyed or disapproving.
As another example, imagine that your sister just told you that she was dating someone who you think is really unattractive and has a bad personality. In this situation, you might ask:
You should also note that you can use the word "seriously" in a complete sentence. For the situation described at top, you could ask:
Is he seriously going to make us throw away the last two months of work?