Haven't played other DMC games, but I had contrary experience with Devil May Cry 4. I wasn't really impressed with the game while playing Nero, but really liked the mechanics while playing Dante.

Play games for less time in one sitting, and you'll get more enjoyment and play time out of them over a longer period of time. It's only natural that you'll get burned out on a game if you play it for hours on end.

I'm playing through Red Dead Redemption and  just got into Mexico and for some reason I don't have a real desire to go on.  Mind you I played about 8hrs of the game over 2 days (6.5 hrs on the first day) and think the game is OK.  I'm not hating it, but not really loving it either.  I find that when I play some gamea, when I get to a brand new world with totally new stuff to explore or people to meet, or when I get to a part in the game that has a different gameplay mechanic, or I get to a part in the game that is tonally different from the previous parts of the game, or part of a game that is just 10x harder than the game has been, there is a good change I might stop the game because I just don't want to play it anymore. 
 
The first time this happened (as I can recall) was Grand Theft Auto III.  When this game first came out I loved it.  I loved Liberty City and loved the exploring, carjacking and the openness of missions.  But then I got to the second island, and never played the game again.  I think the my problem with that game was that I knew the first island well enough to get around and when I got to the second island (and knowing there was a third out there), I just didn't want to learn a brand new map.  GTAIII didn't have that handy "green line" GPS directions thing that IV had (or that RDR has) and knowing where things were was very important in the game.  You had to have an idea of where the paint shops were, where your house was, etc... because you had to drive there.  After getting a handle on where things were and getting into GTAIII, they open a new island and I really didn't feel like learning all new locations so I never played it again.   I suppose I like just playing games, and not learning maps (hell I barely know my way around Denver and I've been here 4 years).
 
The next game I quit mid way was Resident Evil 4.  Once again, was really loving the game.  I enjoyed the atmosphere and the shooting.  Then I got about half way through the game, into the chapel where instead of fighting peasants you were fighting crazed monks.  For some reason I found them much creepier, and they seemed a lot harder to beat.  I didn't like the jump in difficulty and to tone was just too creepy for me (I am kind of a wuss when it comes to horror).  Anyway, never played the game again. 
 
The last game I can think of (before RDR that is) was Devil May Cry 4.  I loved this game.  I loved the combat and really had some sweet combos/strategies with Nero.  Then on the first Dante mission, everything changed.  All the strategies you had for the enemies no longer applied (as you longer had access to the "hand" that was integral to Nero's combat), and not only did Dante have a new set of moves, he had 4 totally different styles with all new combos to learn.  And instead of gradually letting you learn them as the game progresses, they just kind of give you a whole bunch to learn at the same time.  That coupled with the fact that the enemies were a bit stronger than in the beginning, and that they required new strategies to beat was all too much for me to wrap around my head.  So I never played the game again. 
 
Does this happen to anyone else?  Does anyone get mid-game fatigue?  I feel like this happens when a game isn't paced to my liking.  In an open world game, I would prefer to have smaller chunks open up rather than an entire new continent.  I would rather gradually learn one character than having to switch to a new one mid-game (especially if I have to learn all new mechanics).  I would rather have subtle changes in tone, than radically changing the feel of the game.  Perhaps its because I'm older now and really do not like to be frustrated in games.  I do enjoy a challenge, but retrying a level/mission 10x over and over again just isn't fun like it used to be.  I'm playing games because I like the gameplay or enjoying the story.  Having to brute memorize levels just to have a chance no longer has much appeal to me.  Perhaps it is pacing.  If developers kind of gradually made changes to the game, then perhaps I wouldn't have noticed.  If a game ramps up difficulty well, perhaps I would feel like I was prepared for a new area, instead of being overwhelmed and wondering what the hell happened?  Not sure.  I'm sure I'll sit down and finish RDR soon enough, but right now, I just don't have a real motivation to go back to it.