I have essentially the same issue as fkellogg. I'll be working in a drawing and then it stops being able to select objects. I also have had this issue across multiple versions of ACAD and across multiple PCs. The thing is that I can replicate it.
It happens when I'm editing objects and making changes in the properties pane. Most often, I am editing locations. If I select objects and edit their X and/or Y coordinates, after a while of doing this, objects become unselectable. I tried doing some statistics on this and, after 3 tests, I came in around 110-130 X/Y coordinate changes, in the properties window specifically, cause objects to become unselectable. Using the move command doesn't seem to trigger it. Changing colors also doesn't seem to trigger it.
The steps will be something along the lines of:
1. Select block.
2. Edit X coordinate in properties window and hit enter
3. Edit Y coordinate in properties window and hit enter
3a. Often I'll edit other things such as the layer or a color or a dynamic property value, but I haven't specifically been able to correlate any of these actions to the problem since they happen far less frequently, X/Y/Z coordinate changes seem to be the primary culprit, though perhaps it is any change in the properties window.
4. Hit Escape to deselect block
5. Select next object, such as a line
6. Edit Start X coordinate and hit enter
7. Edit Start Y coordinate and hit enter
8. Hit enter because Start Z coordinate is selected but I don't wish to edit it
9. Edit End X coordinate and hit enter
10. Edit End Y coordinate and hit enter
11. Hit Esc to deselect object
12. Continue similar process with other objects until suddenly I cannot edit something or deselect the current object
I can no longer hit Esc to deselect, make changes to the object, or select new objects. I can save the file, which automatically deselects the object, but afterwards I cannot select any new objects. To fix it, I have to close and reopen ACAD.
Its obnoxious because I like to occasionally tweek various layouts of my drawings. Sometimes I'll be editing the positions of a few thousand objects and, every half hour or so, I have to save and restart ACAD because it locks up like this. I've been searching for solutions for years and they always say things like reinstall AutoCAD because it is corrupt. But it has been an issue across multiple versions of ACAD and multiple computers, always exactly the same. I cannot for a minute imagine that it is anything but some sort of memory leak style bug in the interface. It isn't an object count issue because I'm selecting one object at a time and changing a total of 50-70 objects before it finally stops functioning.
The total number of objects selected and edited is eerily close to 64 (50-70). The total number of X/Y/Z coordinate changes is eerily close to 128(110-130). The total number of changes of any type is kind of close to 256 (200-230). But it is never exact from what I can tell so I haven't been able to draw any specific conclusions. I only know to expect this to happen when I'm doing this type of work.