I have to say that if you have a modern spec PC... without any third party programs or using your graphics card control panel, Prototype is extremely painful to play. From what I've been reading so far, a lot of people have been having various issues such as the game failing to detect graphics cards that have higher than 2GB (an issue I ran into), frame stuttering, mouse lag/broken mouse movement (sometimes the mouse will not register movement), and sound issues. I've done a little reading, researching, and tinkering and found what works for me, so I figured I would pass on my findings for the number of issues I have experienced and ones that I am aware of and familiar with. First, let me post up my specs so you guys know what kind of system I'm working with.
CPU: Intel Core i7 Quad Core 2660K (2nd Gen i7)
GPU: EVGA nVidia GeForce GTX 660 Superclocked 3GB
OS: Windows 7 64-bit
First of all, there is the resolution bug where it will not detect your graphics card if you have more than 2GB of memory. Me, running a GTX 660 3GB, it was obviously the first thing I noticed the moment I went into the options screen after I first launched the game. So, I did some reading on several forums and came across this solution that EvilDasterd posted up here on the Steam forums. You go to this link > http://www.wsgf.org/dr/prototype
< , download the "Prototype_All_Res.zip" file under the "Solutions & Anomalies" section. You unzip that file, extract, and copy "prototypeenginef.dll" to your Prototype folder in your Steam Directory. The only drawback there is to this is that you can't change your resolution from the in-game menu. All other settings seem to work fine without completely undoing the fix. With this fix, I would recommend disabling your Steam Cloud Sync to keep it from potentially overwriting and undoing the fix, as I have found that it does the same thing with my edited config file for Doom 3. Also, if anything goes wrong with this file... If it glitches up your game or causes it to crash to desktop, you can always delete it and retrieve your old one by repairing your install.
The next fix is quite a crucial one to those of you with low frame rate problems (in the teens or worse. These problems are not unique to this game alone, as the original F.E.A.R. and Condemned: Criminal Origins also suffer from this same bug. For whatever reason, HID devices will leech or restrict the resources needed to run these games. This is most common with Logitech keyboards and mice, as I found with my G19 keyboard, and G9X mouse. You will have to disable all the "HID-compliant device"s in device manager in Human Interface Devices, excluding the ones that allow the basic functions of your mouse and keyboard. Yes, if you have more advanced keyboards with LCD screens and such, you will have to do without those features as you play. But there is no other work around for this. At least it will upgrade your copy of Prototype: Slideshow Edition to the standard game. :P
I see several issues here in the forums about frame rate stutter and broken mouse controls. I did a little digging on this and the only fix I was able to find was by limiting the frame rate to about 30FPS. Running at higher frames tended to yield bad results. Lots of frame stutter regardless of having V-Sync on or off, and sometimes my mouse would not register movement. This is also not the other game that suffers from this. The original Dead Space I had to cap to 30 FPS, otherwise the mouse controls would break in a way that would make them too weak. Not quite like Prototype, because Prototype's mouse controls will quit registering for brief periods, which makes it just as frustrating when you're in a pretty heavy fight. In order to do this, there are several methods. I'll go over mine. I use the RivaTuner Statistics Server tool that I got with my EVGA PrecisionX. I add it to the list of programs to give it its individual settings, and raise the detection level up to medium for it only and type in 30 in the Frame Rate Limiter field. Make sure that Prototype's .exe is selected, otherwise if you use "Global", it will apply to every game or 3D-accelerated program you run. I found that in running Windows 7 Service Pack 1 that RTSS will rarely work on anything, so if you desperately want to play this game with some stability, you will have to downgrade from SP1 to the base installation. Also, when you run a game at 30fps, you may see considerable mouse input lag. To remedy this, I use my nVidia Control Panel, and set the "Maxiumum pre-rendered frames" to 1. This will minimize input lag and make playing at a 30FPS rate more bearable. Remember to do this for only the process or .exe instead of through Global Settings, unless you intend to use that exact same value on everything you run.
And also... for those of you having audio issues, be sure to set your sample rate to no higher than 24-bit/48Khz, or 24-bit/44.1Khz. If you're having issues with audio stuttering or high pitched "chipmunk" voices, this should fix your problem.
If anyone else has any fixes feel free to tack them onto this post. I'm sure this will make looking for solutions to fix this game less problematic.