In my experience one cannot decide in general wether an application my be started twice or not. It may be for instance perfectly valid to start the same application if it is started in another folder or under another user account or whatever. On the other hand it might be the case that two different applications may not run together if they are started in the same folder or so.
So besides the different approaches with mutexes and semaphores and handling race conditions, it is the wise selection of the mutex's or semaphore's name that handles the above combinations appropriately.
If an application may not run twice at all, take a GUID like name. You can even use the exe's filename if you can ignore that someone might rename it.
Restricting the one-time-start on a specific folder, you can take the exe path into account, but be aware that due to mappings different pathes may end up at the same exe.