Installation on USB or Cloud

Hi,
I've been running PortableApps from years on a USB drive and different PCs assign different letters to my USB drive, so sometimes the Platform runs on D:, sometimes E: etc.
I've found no big problem. Sometimes a program tells me not to change drive letters, but works fine in spite of it. The main problem is opening a recent file that should be on D:\Documents and now is on E:\Documents, but nothing to worry about: just go open the document in its new place.
So if you move the platform, I think (as a user) that you won't face big problems as well.

About settings to increase performance, I think it will depend on drive speed only. Running Platform on a internal drive will be faster than in a USB drive, mainly if it's a SSD internal drive.

In case of OneDrive, be sure that files are in your local drive (a green check mark on each icon), not only on cloud (a blue cloud mark on files). Files on cloud will have to be downloaded before running, so it takes time depending on your connection.
It is a very intricated setting, because having files on cloud saves disk usage (therefore are recommended). I can't figure at this moment a way to tell OneDrive which files will be put on cloud and which will remains on local drive. Maybe if you right-click on PortableApps main folder and choose "Always Keep On This Device" all files and folders inside it would remain on local storage.

Anyway, I'm not an expert nor in OneCloud nor in PortableApps code. All this is just based on my daily usage. An I hope it helps.