I can't say as I have ever thought about it. I have an action that places 50% guides for illustration type documents, and I just run it and use what it gives me. But I just started a new document at 1501 x 1201 and ran my action. I set my rulers to Pixels, and zoomed into 3200%. The vertical guide was dead on 750.5 so it split the pixel (from a display point of view. But that is not really relevant, so I zoomed out to actual pixel size, and the guide was on 750 - an even number.
But I guess that what is important is how objects will snap to those guides, and the default seems to be that a one pixel line (Shape) aligns on the left of the guide. The only way I could force a line to snap to the other (right hand) side of a vertical guide was if there was already a line on the left. Interesting, but not particular helpful.
My greatest hope right now is that my little foray into the dreaded realms of pixel-peeping won't leave me obsessing over the precise (as in pixel perfect) placement of objects, although I can see times when it would be visible, like with free transform step and repeat where an error could build up, or when making arrays and spacing patterns.
Do you have an end result/target in mind where this critical?
Looking back at my first paragraph, I wonder if Photoshop is doing its calculations at a better than pixel level, and rounding to the nearest pixel. That would make sense. Rather like Excel where a value might be displayed to two decimal places, but for the sake of calculation, Excel has a shed full of decimal places to represent the precise value of the displayed number.
Seams I recall either photoshop or illustrator had a snap to pixel option. I can not remember which one, but if it photoshop, that would cause this issue.
I've been doing a little experimenting, and the results are mixed. It does (possibly) seem to be related to the resolution/aspect ratio of the image. So for example, at 2560x1440 it only goes by even numbers, no matter if the guide is vertical or horizontal. However, when I created a new document that was 1600x1200, it allowed me to drag guides out to half pixel locations. So maybe you're onto something with the way that Photoshop calculates placement.
Yes, I am trying for pixel perfect alignment. The whole point wasn't anything critical - Google now has new guidelines for the cover art on Google+ Pages and Profiles. They released a template that is 2560x1440 and marked it off with the resolutions for each device a YouTube channel will be viewed on. Their template was okay, but I wanted to drag guides onto it over each section so that I could resave the template and take advantage of snapping to guides for placement of elements so that I know for sure they'll display properly on the device I'm designing for.
So in other words, the text and logo safe area is 1546x423, an oddball number. On their template, it's right smack in the middle. It would be easier if I could draw a marquee around that using guides so that I stay within the boundaries. Then I could expand to 1855x423 for tablet resolution while still in the same template file. This way I can design one image but make sure nothing important is displaying out of bounds for mobile, yet not just fill the expanded area with empty content for the sake of taking up more resolution for tablet.
I've recreated the template by making the original document 1546x423 and dragging guides to each edge (which Photoshop seems to do fine, even if it's an odd number pixel count) then I expanded the canvas to 1855x423, dragged guides to those edges, repeat for 2560x423, and then repeat again for 2560x1440. Whew! A lot of work for something as simple as just dragging guides out.
Anyway, the mystery continues as now in full res, my guides are not on the same pixels as they were when I drew them. After the final resize, it's off by a single pixel. I'm still not clear as to why, but I think it's related to what you said and it's almost a sort of rounding error.