Hey,
ok, first - a hefty proportion of your investing should be in (home country) stocks - simply because it has the most direct impact on you, vs inflation etc. Especially with the UK, which has a nice reasonably diverse core pair of indices (FTSE 100 + FTSE 250 - former is multinationals and large companies, latter is more domestic stuff). One HUGE thing with the S&P 500 compared to most countries' headline index is that the S&P (like the FTSE100) contains a lot of the true global companies. For Americans, the S&P is a double win there.
So, that aside (and ignoring the VUKE.L vs Irish-domiciled ETFs like HUKX.L - so, the former is a wrapper for a UK fund holding the FTSE 100, meaning withholding tax is paid in the US; for the Irish ones, none is. However the MER on VUKE is lower than HUKX... I haven't figured out which is actually better, but I'm tending towards the Irish).
The S&P 500 IS US holdings, so you will need to fill in a W8-BEN form with your brokerage in order to get only 15% divis withheld not 30%. And yes, it'll all fluctuate as the $ does against the £.
If you search for a post by Grace I think, I gave what I thought was a pretty good passive portfolio! Or at least a starting point - you have to know what your goal is, what your risk tolerance is, etc.