Firstly I should classify I've never played RE4.
Starting off, this is very clearly a well polished game, the great art, music, SFX, little effects like the enemy knockback all go towards creating a great feeling game. A puase button would have been helpful (especially for taking notes on my thoughts on the game) but aside from that there wasn't much of an issue.
The issues come more so from the gameplay. The very contra-esque gameplay is quite fun and the game introduces new enemies and obstacles at a good rate. The big problem for me is that the game doesn't take into account a new players perspective very well. So much of the game feels like it would be fun and challenging if you know what you're doing, but when it comes down to actually playing it and learning the challenges for the first time it feels cheap. I have to die learning the strange ins and outs before I can then die actually trying to beat it. I like challenge but at this point it's not fun and challenging just tedious.
I'll break down some examples.
First is the axe throwing enemy. Whilst not a bad enemy in itself, it doesn't fit with the fast paced gameplay. It's the type of game where thinks happen very quickly and you need to be able to respond quickly, but then the axe guy comes along and you have to figure out he has a very slow 3-cycle. Not out of place in say Mario, more so here. Then each subsequent encounter I can't tell at a glance where he is in his cycle, unless I've already played the part several times before I have to stand around and figure it out which is incongruent with the game's "GO GO GO" nature that's key for survival. At the point past the bridge collapsing I stopped to take care of threats which didn't directly screw me over, but this lead me into a situation where the axe guy, bear trap and stabby women combined to make a situation that was almost impossible to get past. Then I'd die and come back, only to discover I was meant to just keep going non stop, else I'm screwed forever. Perhaps if everything was better synced up or the stabby women spawning had some consistence I could figure this stuff, but so much of that information is pretty much invisible to the player.
This brings me on to another couple of this. The first one is probably a little controversial, a wider screen width. I get that you wanted to be NES faithful and fast reaction is part of the game but it does go towards keeping info from the player that they'd only know had they played the game before to a wearing degree. Even Shovel Knight, known for being strongly NES inspired had 16:9 res. Keeping the box-like resolution reminds me of that Yahtzee Croshaw quote "It was like going to the renaissance fair only catch the bubonic plague and have the kind shag your wife".
The second issue being the lack of recovery. To go back to the Contra comparison, in contra (Super C and Alien Wars at least) when you get hit you disappear before you come back flashing, giving the screen time to clear. Here, if you get hit once then even if you come back flashing you're already overwhelmed by that point and are likely to take a hit again.
Overall, I should clarify that the game is really well made and the gameplay is fun when you know what you're doing, but a lot of it feels like if you try one approach but it wasn't the "intended" approach then you're screwed without even knowing it. It's almost bad adventure game like in that you need to know the one intended solution and any other seemingly valid approach falls apart due to lackluster information provided.