I bought MSTS yesterday and I installed and played it. I closed it to eat dinner and came back to play and I got in the game and loaded up a mission only to find out the keyboard no longer works! The only way to get out of the game is to Ctrl+Alt+Delete out of it, when task manager comes up I saw the CPU usage read 100%.
My system is....
Pentium 4 2.2GHz
256MB ATI Radeon 9250.
I have MSTS installed on my 250GB external HD. I know it's not the HD because I have FSX, BF1942, SWBF2, Lego Star Wars 2, LOMAC, JetFighter 2015, MX vs. ATV, SC4, and Civilization IV on the HD and they work flawlessly.
Try defragging all drives and rebooting.