Primarily, EGB suffered from two fatal flaws for me. One is typical of a lot of shows that don't find an audience, the other is more of a Ghostbusters franchis flaw.
1. The first flaw - forced characters. Sometimes in an effort to promote diversity, a show can come off as a little too PC. No matter how good the writing, audiences often have a hard time overcoming this flaw.
2. The second flaw - destroying the original premise to get an idea over. This is a lot of what plagued the second movie. Let's take a concept that is essentially a buddy/character movie that people buy into and blow it to kingdom come. RGB was the “natural” sequel to Ghostbusters. The guys continue doing their business, sometimes scrapping by, but sticking to the original premise.
GB2 basically said “yeah everything went to crap and now they have to start over.” Clearly that idea didn't resonate with people. So why would you create a TV series with the same concept?
Why is it that for 13 years, the best “future” anyone could come up with for Ghostbusters was to put them out of business? It's like taking a giant crap on everyone who bought into the original premise.
GB the video game got one concept particularly right in that regard - people die every day. In theory a Ghostbusting company would be expanding, not shrinking.
I do believe there were other factors at work as well.
Kids were changing and EGB was too late for Saturday morning or even weekday afternoon cartoon's prime, and they were too early for adult swim and some of the cable network animation that has come online in the last few years.
Not enough time had passed. The reality is that the death of RGB was only 6 years prior to the launch of EGB. People didn't really have enough time to miss the concept and perhaps more important, the generation that grew up with Ghostbusters and RGB was not old enough to be in a nostalgia phase (which is what you're seeing now with males in the 25-35 age range).
All in all, EGB is a good show. I just don't think it can compare to the first series. It was RGB's version of Batman Beyond.