Nothing to talk about
You should realize that there is something wrong when the two of you have nothing to talk about. While it is recommended that you work towards fixing any issues, you must know when to call it off.
People change with time. You might have fallen in love with him/her in the past, but he/she might have changed over time, adopting habits you dislike. It is healthy to discuss these issues, but if your partner fails to change, you might want to call it quits.
Once you two start keeping secrets, the relationship is pretty much over. If you feel the need to keep secrets from your significant other, you should reconsider the relationship seriously.
The desire for freedom
If your partner is very possessive, and has gotten worse with time, you might start feeling trapped. Your freedom comes before anything else, and if you are in a suffocating relationship, it is time you break it off.
Unable to connect with the partner
If you no longer feel any connection with him/her then it is time to end the relationship as well. Being connected means you can always talk to them whenever you want but if he/she appears too busy or least interested in what you have to say, consider that your relationship is reaching its end.
If the two of you are no longer comfortable with intimacy, you really need to consider whether both of you are really into the relation. If not, it is better to part ways early than drag it out.
No desire to make things work
Couples fight, but that doesn't mean they have to end the relationship; however, if neither of you want to make up, you have a problem on your hands. In the early stages of the relationship, couple like to resolve their differences quickly after a fight; however, later the urge to mend fences can disappear.