I know, flash back to 2007 or so. 
Just bringing this up as it seems to be affecting me, but is there a particular file format for the usb to run portable apps best?
I ask because a few weeks ago I had to get a new usb because my old one went dead and the file format of the new one is exFat.
Since then, or around then, using Firefox and Thunderbird has been slower to load up or it hangs every now and then. It has even recently been crashing after I try to close it and it hangs.
It could be just some extension, but it happened so soon after I switched to a larger usb, a kingston dtse9 64gb. My previous usb was a Silicon Power 32GB Jewel J80 and I forget what file format that one was.
It's just firefox and thunderbird that seems to hang longer, which makes me think it is the many tiny reads & writes.
Transferring single or multiple big files seems fine to me
Firefox and Thunderbird work fast and fine when it is my backup copy on my hard-drive. USB was slow.
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FAT32 for drives up to 32GB, then exFAT for drives 64GB and larger.
As for the slowness and hangs, it is possible your new drive isn't as fast as your old drive. It is possible the new drive could use some defragging. It is possible the new drive has some broken clusters.
Ed
Just to mention: any kind of defragging on flash drive is completely pointless in contrary to rotating magnetic hard drive.
exFat is ok, but there are still some cases when it not recognized. Therefore also 64G drives I am formating to FAT32. It is just windows does not do it for what ever reason. You can use in such case something like: http://fat32-format.de.softonic.com/
But there are many utils for that around.
Otto Sykora
Basel, Switzerland
http://www.ridgecrop.demon.co.uk/index.htm I have a 64gb corsair survivor and normal format processes only recognize 32gb of the drive. I may be wrong, but it appears to be constructed of two 32gb chips and this is the only program that I found to restore it after a Wins format rendered it to 32gb. It's called gui format.
http://www.ridgecrop.demon.co.uk/index.htm?guiformat.htm
there are many programs around formating sticks. Only windows refuses to format it to more then 32G. The guiformat is just so simple as it is one exe with no extra functions, so no installation etc needed. So in fact portable ;-)
Otto Sykora
Basel, Switzerland
How fast is your USB drive? This can tell you:
https://portableapps.com/apps/utilities/crystaldiskmark_portable
Report the speed back as it could be a slower drive or a bad or counterfeit one.
Sometimes, the impossible can become possible, if you're awesome!
I own two of the DTSE9 USB 2.0 drives and their read and write speeds are horrendously slow. I now have them as souvenirs because of their small size and solid uni body structure. I only use USB 3.0 with my portable apps, and thats even on a USB 2.0 port. I'd look into something thats USB 3.0 for starters, Kingston does have a 2nd Gen DTSE9 and it's in USB 3.0 and called the DTSE9G2.
Also, to touch on what John suggested to test your read/write speeds. You may want to give rufus https://portableapps.com/apps/utilities/rufus-portable a try and run the bad blocks option to verify you have a drive with no bad blocks on it. This is a method used to gain some insight as to whether or not your drive may be a fake, for example you buy a 32GB drive but you're only able to write 16GB of data to it, and it's also used to determine a failing drive.
I forgot to mention, you wont be able to test the drive in question if you run the application from it, so install rufus locally or on another flash drive to test the drive.