Only region I've sat through from beginning to end was Kanto. I saw through a lot of Johto during the supermarathon a few years back in the leadup to Diamond and Pearl, saw the beginning of DP, and haven't watched much else. I could go by ratings, but then again, that would be unfair, as each series gets progressively worse ratings.
From what little experience I do know about the various series (note that Johto was not included in this since that's technically part of the original series), I'll rank them from worst to least worst:
1. Best Wishes.
2. Advanced Generation
3. Diamond and Pearl
4. Original Series
As I have little knowledge on XY, even for someone who hasn't watched any of the recent series at all, its not listed on here, though I'd probably place it either between AG and DP, or otherwise right before Best Wishes.
1. Best Wishes was, without any doubt (other than possibly XY), the absolute worst series, period, from what I could gather. They had to shatter continuity, make Ash into a complete idiot, even more than in prior series, Team Rocket, despite being upgraded from wimps, still wasn't handled right, they had Ash not only lose the league, but actually decrease in rank for whatever reason, and they gave him the Team Rocket treatment with Trip. Yes, people can argue about Paul, but at least he actually did have three regions worth of experience on his belt and actually did know what he was doing. Trip was a rookie and really shouldn't have been able to beat Ash that easily. Their inclusion of Dawn was also completely random, as she literally had no reason to be in the region. Misty at least already didn't like having to run the gym and left at the first opportunity and wanted to meet up with Ash anyways, and at least May had a specific trans-regional ribbon to aim for as an excuse for her appearing in Sinnoh. Plus, when exactly did she qualify as a Pokémon Trainer than a Pokémon Coordinator? Also, for a so-called "advertisement" of the games, they really dropped the ball in advertising aspects actually from the games, specifically the World Conference, which would have killed two birds with one stone by a. showing something from the games, and b., actually giving the perfect excuse for Misty at least to reappear. Probably the only good things about the region are that Iris at least wasn't given the characterization of an airhead, unlike May and Dawn, and that she actually was allowed to pursue her goal, unlike Misty, the only other female main protagonist that had a goal that wasn't that of a Pokémon Coordinator, and they at least actually acknowledged Ash's original Kanto team, including Butterfree and Pidgeotto/Pidgeot. Ash being listed as ten, although unfortunate, isn't really an issue because really, most official materials listed Ash as being ten, yes, even AG and DP.
2. Advanced Generation is the second worst. Literally the only reason it's not the worst right now is because BW managed to top it. The Gym Leaders were treated like total pansies to Ash's rookie team barring Pikachu (which makes their decision to force Misty into a gym even more insulting due to it giving the implication that the Gym Leaders were extremely weak, almost to Team Rocket Trio levels), Team Rocket basically suffered from wimpification even more than before (only DP exceeded that bit, and at least there, they gave Jessie some redeemability by making her a skilled coordinator), and they made May into... I know its an insulting phrase but I can't think of a better word right now... a bimbo, just like the characters from Love Hina, Battle Vixens, and heck, the Fiorello Fangirls from the original series. It made the sad situation of their replacing Misty even worse when they effectively insulted her character (she was pretty much one of the few Anime characters who DIDN'T fall under that characterization. You can thank Princess vs. Princess regarding how I knew that). Honestly, I could forgive May replacing Misty as long as they didn't make her into a character we would expect from say... Love Hina, Battle Vixens, or heck, Maron from DBZ (by that, I mean Krillin's girlfriend, not his daughter with Android 18). Also, May proved to be a bad mother in the final movie when she basically didn't even attempt to rescue Manaphy at all in the climax. At least send out your Squirtle or your Beautifly if you can't reach him. Honestly, she was a coward who abandoned her own kid. Also, Ash ended up not improving in the Hoenn League (IE, increasing in rank), which until BW was the absolute worst League result that ever occurred. And as shown with May's departure, the group lacked any real chemistry. Oh, and they also decided to bring Brock back despite the situation at Pewter gym being even worse, and what's worse, when a repeat of what happened beforehand at his gym occurred again during Battle Frontier, despite his family proving again that they simply aren't cut for the gym, he basically irresponsibly ditches the gym, again. Brock doesn't even focus on his breeding goal. It was also the start of the girl-swapping for eye candy purposes as well, and May was especially blatant where her appearance was more befitting of a teenager than an actual 10 year old.
3. Diamond and Pearl was a bit better than AG, though not by much. Dawn showed some promise in the beginning episodes of not being an airhead, although the moment she complained about bedhead ruined it. Team Rocket was pretty much shown to be pathetic, with their having two of the worst costumes in the entire franchise in this series (and by worst, I mean they were extremely pathetic, obvious costumes that absolutely no one with a brain could even mistake them for someone else). They were innkeepers (who wore a green coat without even covering up the tell-tale "R"), and a Croagunk (Meowth, who fooled everyone in the area, even Brock, someone who actually HAS a Croagunk, and not only that, was voted the best Croagunk despite his disguise being extremely obvious). And Brock literally had no reason to join the group other than due to the trucker leaving him behind. The good news is that the Gym Leaders were actually shown to be challenging, though not quite to my expectations (as I was hoping Pikachu would sit it out since its experience would outrank the others, not be pulverized especially considering its win against Regice). And Ash actually increased in rank. Too bad he still lost the league, but at least he showed signs of improvement. In addition, Team Rocket's wimpiness was mitigated somewhat by Jessie actually proving herself to be a skilled coordinator.
4. The Original Series was by far the best series, yes, even Johto. Kanto had Ash beginning his journey, and his losses can be justified as well. In addition, the group dynamic actually worked. The Gym Leaders were actually shown to be somewhat difficult. Team Rocket were shown to be genuine threats at various points rather than wimps, and even their disguises were at least done well enough to make it look like they are different people, thus not leaving the main characters to be complete idiots. Ash also improved during Johto to not get freebies as well, and overall the journey actually seemed somewhat realistic, and he actually does improve in regards to the leagues as well. And honestly, watching the Johto so-called "fillers", I didn't see what was so bad about them. Probably the only real complaints I had were Brock's womanizing a few times (though it certainly wasn't as bad as his instances of womanizing in the AG and DP series) and their really insulting removal of Misty at the end of the series. Other than that, there wasn't exactly much bad about them. Maybe Orange Islands wasn't too good, though.