If the system is also compromised, a second opinion scanner wouldn't work - if the malware is not from a script kiddy. Only live medium scanner works as real second opinion, which works without active running OS
@silversurfer is right - in most cases, there will be not much difference in detection between second opinion scanner on Windows as compared to using a live CD. Second opinion scanners could find out the infection traces many times on Malware Hub (even for sophisticated malware).
Anyway, there are rare kinds of malware that can make a difference
in the postinfection stage (rootkits, malware that uses anti-hooking, malware that can block/restrict Internet access, hide Registry keys, etc.). Furthermore, disinfection can be more comprehensive when using a Live CD.
Edit.
There are some advantages to scan files when the system is running. For example, some malware can remove the traces before the system is closed, and start the infection chain after reboot.