Trying to watch The Wire today is sort of like trying to watch Pulp Fiction for the first time now and not understanding what the big deal is.
It was incredibly unique at the time, a cop/crime drama that played by none of the rules, and dealt with ideas and concepts that just weren't depicted at the time. Between the overall hopeless nihilism of the whole thing, no clear good guy/bad guy, the willingness to serve up complexity and ambiguity, and the anthology nature of it, there really wasn't anything like it.
You can say that Tony Soprano was an anti-hero, but he was always the hero of that show and world. The Wire was much different.
I've never gone back and revisited, because I just don't do that, but I'm sure having a thousand shows since then that built on it's legacy certainly would make it hard to appreciate. I think Game of Thrones is directly descended from it in a storytelling perspective, with obviously a ton more eye candy. For example, the way The Wire killed off or marginalized apparently main characters was totally unheard of at the time, but is now pretty common...it wouldn't even register today. There was a whole "I can't believe this is happening on a TV show" vibe watching it early on that would be completely unremarkable today.