How I have successfully done this (i.e being able to switch instantly between VSTs) is to load a project group using the SWS extensions with one project tab per patch. (I have loaded up to 20 tabs with some fairly large VSTs with samples on a 2G machine. I'm not sure how much memory sharing goes on in this situation but there seems to be some, in that two instances of a VST with a several hundred meg piano patch don't seem to double the memory. I'm still investigating exactly how many patches I can load, but I would think quite a bit more than this, particularly using synths like Dimension Pro which are fairly reasonable in their memory requirements.)
Then I use MIDI-OX/MIDI-YOKE to convert the patch change messages from my master keyboard to MIDI CCs. This is because currently Reaper's MIDI action functionality seems to only work with CCs.
I reserve two patches (00 and 55) as unused on my master keyboard (a Korg X5D) and these are then mapped to the actions for previous and next tab. There doesn't at present seem to be any way of selecting tab (n) by sending a MIDI CC (n) which would obviously be nicer.
However this approach lets me randomly choose patches on the master keyboard without changing the computer-based patch, then if I select either 00 or 55 on the master keyboard, I can select prev/next patch on the computer. Since usually you know the set order, this is manageable if not absolutely perfect.
If your master keyboard has no inbuilt sounds (you're braver than me, for live use), or if you're playing guitar, and therefore using Reaper as a switchable FX chain this way, then you could just assign program change up and down through MIDI-OX/MIDI-YOKE to two arbitrary MIDI CCs and then assign those to previous/next tab, of course, rather than my 00/55 trick, because this suits my master keyboard more. (I'll assume, as a guitarist, you're using some kind of external MIDI controller of some sort to do this, of course).
Reaper is rock-solid in this mode and you can even change active project tabs while playing, there are no glitches. It also works for guitar effect chains; I've tried this too. The advantage of this approach is that each tab is a completely separate set of layered VSTs plus FX chains, and you can assign MIDI channels to each track in the project easily. Then you can save modified versions of the individual projects if you tweak just that patch.
Because all the projects are pre-loaded, you really can switch patches about as quickly as a hardware synth does - there's no load time because the project's already in memory. Also you can then assign some of the knobs on your master keyboard to track and master volumes - this will let you control the overall volume for the patch PLUS any individual layer volumes, and because the learn is per-track, your assignments will make sense across project tabs. This is harder to do with the 'all tracks in one project' scenario.
Another advantage is that if - worst case scenario - Reaper crashes, you can always load just one project at a time, e.g, a generic piano patch or something you can use; time is of the essence in recovery. Whereas the giant project approach is an 'all or nothing' situation since you have to reload the whole project. Also you are using just as much memory, if you load a VST on multiple tracks; you may as well use projects instead, IMHO.
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