I'd try a different x264 CPU Preset, beyond that I'm not too sure hopefully someone more knowledgeable comes along.

I've tried everything from faster to ultrafast, with no change whatsoever. Also, I've tried NVENC (what I'm currently using) and most of those presets. Same deal.

I'd suggest fucking around with your graphics card/display settings in Nvidia control panel. Issues like this seem like they're more likely an issue with graphics card settings. Pre-rendered frames (lower if possible) might be something you want to look at as well as display scaling (No scaling might help). Also try updating or rolling back graphics card drivers.

Pre-rendered frames is set to 1 (lowest), and there is no scaling going on in game or via nvidia control panel. Also this has been an issue ever since I've been streaming, and numerous driver updates have happened since then, so I don't think rolling back would help.

Thank you for your input though! I'll continue to play with Nvidia CP and see if anything changes!

It's also worth trying to stream in games that aren't tf2 and seeing if the frame skipping/input lag issue persists. If they don't it might be something to do with TF2. There are some optimization commands related to cpu/gpu usage. Might be worth checking those out or getting rid of your config and testing on default settings.
If you're really stumped, r0ach on overclock.net also has a guide to optimising mouse input for windows. A lot of this I think is placebo and doesn't actually help. I wouldn't reccomend fucking around with the bios settings, but the software section as well as the win 10 section might be worth looking into, don't count on it doing anything though.

So far it seems the only other game that gives me issues is the Division, but I've only tested a handful (BF4, Warframe, etc). Witcher 3 runs fine for example, the hitches/mouse resistance isn't there.

I'm also not sure how much that mouse guide will help, because my mouse is normally 100% perfect, at all times except when streaming. However, I will be giving it a read.

Thank you though! I appreciate the response!

Definitely a TF2 issue then.

Are you running it in DX8?

If you're in DX9, do you have Aero Extensions enabled?

Do you run in full screen, windowed, or a borderless window?

Do you have multiple monitors? What's the refresh rate on each one?

DX9, not sure about Aero because I was under the impression Aero wasn't a thing in windows 10, unless you mean Aero in reference to something tf2/OBS specific.

When streaming, I play in fullscreen. Borderless windowed while streaming is a nightmare.

I have 2 monitors. The main one (I play tf2 on) is a 165Hz 1440p Gsync IPS (ASUS PG279Q). Second one is a generic 46" LCD TV @ 1080p 60Hz.

Aero is in everything after 7. Aero isn't necessarily the theme - it's really called Desktop Compositing. Aero Extensions are an option in the TF2 advanced video options menu. They should be turned on at all times in DX9.

For the sake of testing, can you downclock the PG279Q to 120Hz, or disconnect the second monitor? One or the other, doesn't matter which.

Downclocked the PG279Q to 120Hz and the problem persisted. Unplugged the second monitor and my PG279Q wouldn't even clock above 60Hz, strange.

try using nvidia nvenc on encoding settings instead of x264

see post #3

Weird, this happens even when just previewing the stream, but not actually capturing any game.

I ran OBS (non-studio) preview with only twitchalerts, spotify (window, subregion capture), text file capture, but no game capture, and the issues persisted. Essentially I was playing tf2 with the stream running, but not capturing tf2 or any other game, and the issues were still there in tf2.

This is fucking with me on a whole other level now.

Have you tried lowering the process priority of OBS?

TF2 is very CPU-bound and only actually utilizes a few threads. If OBS has a spike in usage and starts using the same core as TF2, it might cause those hitches that are short enough that the framerate doesn't seem to be affected because it's hurting frame times more than frame rates.

At this point it's very clearly an OBS issue that TF2 is more prone to being affected by than other games. All the other games you listed, while being CPU-bound, are fairly heavily multithreaded and wouldn't be affected by a spike in usage on one thread as much.

The thing is, these hitches are consistent. They are always exactly the same space apart and always happen. They don't go away/come back and they don't change their timing.

Lowered process priority class of OBS through all of them and the problem persists. This is what my CPU usage is with OBS process priority class of Idle (lowest), preview running, playing tf2 in fullscreen, while watching a stream. Problem is still there.

http://i.imgur.com/EQuu9Sw.png

I'm beginning to wonder if I should buy an XSplit license, or if this problem will persist through other streaming software.

Are you always watching a stream while playing? Don't watch any vids/streams etc while playing, if you are.

Nope, they are always paused/stopped. This time I left it on just to add some CPU usage.

I wouldn't say this is a TF2 issue. To me it sounds like a streaming with one PC issue. Sure, an i7 will stream 720/60 "no problem" but what people fail to mention is that you'll still have this slight mouse input lag. Go ask any streamer on one PC and they'll admit that they have this issue. The only way to solve it right now is to get some kind of super computer or stream with two PCs. Most people who stream with one PC just put up with it because it's not THAT bad and it's worth it to stream with good quality. I did it myself for two years before buying the second computer.

I'm pretty sure this input lag is one of the reasons why a lot of the top TF2 players don't stream their big matches. They're willing to stream matches against easier opponents because the input lag won't make much difference on the outcome of the match.

I was kinda leaning toward this idea. I was wondering if maybe there was some sort of dedicated streaming hardware I could use, like a PCI-E card or something similar. Maybe a blackmagic or avermedia card, but I don't know much about them. I don't really have the cash to fork over for a new PC, especially since I'll be moving soon, but I might be able to come up with something.

Are there any specific reputable guides out there you could point me to, for configuring/using a dual PC streaming setup?

I might just end up sucking it up because I'm not sure if it's honestly worth the effort.

Most of the dedicated capture cards do have their own encoders built in, but honestly the thing to do is to just put the capture card in a second computer like SLIN said.