Too many seem to have the following structure:
90% of the time is dedicated to an episode specific narrative following a formula. Whether it's the detectives getting a case, the scientific guy chasing a new phenomenon, etc. For the most part the, the events in this portion are episode specific although usually there's some new morsel that exposes information the grand conspiracy and larger story arc when that episode's events are resolved.
10% of the time is dedicated to following/expositing the serial aspect of the story, usually some kind of conspiracy or larger story. Very little information is exposed, mostly just enough to let you remember there's this bigger (and often much more interesting) narrative arc taking place.
Mostly this just feels as if the series has been turned on its head. It should be about the 10% part that is the actual "meat" of the story. If (and only if) the dumb series runs enough seasons, the larger story arc might get resolved in some semi-satisfying way. Mostly it seems like the writer had a pretty cool idea but didn't know what to do with it, and fell back on the "case of the week" to fill it in because the bigger idea really didn't have much behind it.
In some cases, this can be tolerable but most of the time you just feel strung along, like there's this really cool story that's going to get broken wide open...and then nothing, or something entirely lame like Lost happens.
In contrast, really good series (like the Wire) manage to make the entire series about the story arc and the individual episodes expand and bring it out. Part of the Wire's specific genius was that it did this well and also had a seasonal anthology feel to it as the action shifted from the corner, to the port, to the dealers again without losing the larger momentum but giving us different characters and settings, too.
When I start a new series if I feel like I'm being strung along by episode 4 or 5, chances are I won't ever get resolution and I just drop it.