I know it isn't advised to run Qubes-Whonix from Virtualbox due to performance issues, but other than that, is it safer? I.e. is it harder or easier to hack/infect Qubes-Whonix running from Virtualbox than running as usual?
Your security posture is likely somewhat weaker when running it in a VM. I recommend that you read the Qubes-Whonix security page, as it has some useful advice here.
Running it in a VM means you increase your attack surface. Qubes-Whonix itself is designed to offer increased security, so running it inside a VM in a regular OS doesn't make much sense. You're basically running a hardened OS and then giving an OS with a weaker security posture complete control over it. You also shouldn't use a multi-boot environment for exactly this reason.
Additionally, from a forensics perspective, you can't make as many safety guarantees about memory volatility when using a VM. The virtualisation solution may flush some guest pages to disk, and the host OS itself may swap out guest pages too. Data written to the virtual disk may remain in slack space in the virtual disk file even if you overwrite blocks from within the guest, because virtualisation solutions don't always use simplistic block storage models for virtual media.
If your threat model is such that all of your sensitive work is isolated within the Qubes VM, and you're not concerned about someone targeting you personally (as opposed to a drive-by malware campaign), then Qubes in a VM is fine for convenience. Otherwise I'd run it bare-metal.