It's broken (and you can't fix it)
Artwork must be handled carefully and sometimes we damage our favorite works and need something new to fill the void. Replacing a broken or damaged piece is bitter sweet but change can be a good thing!
Your style changed
You are always evolving and sometimes that means that things you previously loved just don't fit your esthetic anymore. That's just fine! You're allowed to switch it up anytime you want without guilt. If you've invested in a nice piece, it will still be nice for someone else so try to sell or give away your quality item. Maybe you can partially fund an upgrade to something that is more your current taste.
You never really liked it
Artwork is a treasure to some and not so valuable to others. If you have a piece hanging that you are silently hating take it down! Artwork is an expression of self and should define your space as a personal statement. The pieces you see every day should make you happy. Keeping artwork around that you don't love is a waste of space.
It doesn't fit
Artwork makes a space brighter or fills a void in a space of appropriate size. Scale is important when finding artwork you love and if the fit is not right the piece wont work for you. If you need to save it for later — maybe it's an antique or a family heirloom — find a way to store it or loan it out to someone with more room, but cramming artwork that is too-big into your home won't help you. Your home is for living, not storage.